Prof. Hölscher’s research is focused on the development of novel treatments for Alzheimer’s and Parkinson’s disease. His group is currently analysing promising drug candidates that show good neuroprotective effects.
Alzheimer’s and Parkinson’s disease are sporadic diseases, which means there is no clear genetic link to the development in the majority of cases. This makes it difficult to investigate this disease, as very little is known about the mechanisms that trigger the progressive neurodegeneration.
However, there are several risk factors that increase the risk of developing these diseases. Those risk factors can give us some pointers of what mechanisms might be responsible for the initiation of the disease.
One such risk factor is type 2 diabetes. Several studies show that people with diabetes have an increased risk of developing Alzheimer’s or Parkinson’s disease. In diabetes, the hormone insulin loses its effectiveness. Studies of the brain tissue of patients with Alzheimer’s or Parkinson’s disease have shown that insulin signaling is impaired. Insulin not only controls the blood sugar levels, but acts as a growth factor to promote cell growth and repair. It is possible that the lack of the insulin effect reduces the repair mechanisms and puts neurons at risk. Neurons cannot be replaced and live as long as we live. Over years, cellular stress could damage neurons and prepares the ground for the development of Alzheimer’s and Parkinson’s disease.
Novel treatments for Alzheimer’s and Parkinson’s disease
When testing drugs that originally have been developed to treat type 2 diabetes, several showed good effects in preclinical studies of neurodegeneration. When analysing the biochemical processes that underlie Alzheimer’s and Parkinson’s disease, we found that drugs that activate the GLP-1 growth factor receptor in the brain showed good neuroprotective effects.
In preclinical studies we could show that the drugs induce cellular repair mechanisms and prevent the loss of synapses and of synaptic function. The amount of beta-amyloid, a classic biomarker for Alzheimer’s disease, has also been reduced. Importantly, the chronic inflammation response in the brain has been much reduced. Neurons that were not working properly anymore started to come back and function normally again. These observations give us hope that we can actually stop the development of Alzheimer’s and Parkinson’s disease. First clinical trials have shown good effects and show that the drugs also work in humans.
For a review, see Reich & Hölscher 2022
Clinical trials
Based on our results, a clinical trial testing the effects of liraglutide in patients with Alzheimer’s disease has been conducted in collaboration with Imperial College London. The results have been presented at the AD/PD conference on 9 March 2021. Liraglutide was able to improve memory and cognition in the ADASexec test battery. In addition, brain shrinkage due to neuronal loss and loss of total grey matter was reduced by the drug as shown in MRI brain scans. A paper with the full results will be published soon. The company Novo Nordisk has announced that they want to test the GLP-1 analogue semaglutide in patients with Alzheimer’s disease in two phase III trials.
Further studies of such drugs in Parkinson’s disease are onging. A recent phase II placebo controlled trial conducted at UCL in London has shown very good effects in protecting patients from the disease. This study tested the older drug from this class called exenatide (Bydureon). Motor control was protected from deterioration by the drug, while the placebo group got increasingly worse. A follow-up phase III trial has started at UCL. Another clinical trial testing the drug Liraglutide showed good protective effects in PD patients (Cedar-Sinai hospital, Los Angeles). Everyday activities such as walking, talking, chewing, getting dressed, getting out of a car, etc. were significantly improved by the drug. Memory and cognition was improved, and the quality of life scores were increased. See the results here.
Other trials are ongoing in France (Lixisenatide, multi-site trial), and Oslo (Semaglutide). Other clinical trials are testing a pegylated version of exenatide called NLY01 or a slow-release formulation of the exenatide called PT302.
The abundance of trials demonstrates the great potential of this research area to deliver disease-modifying treatments that can considerably improve the quality of life for patients.
Contact: c.holscher@hactcm.edu.cn
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A list of research publications
A list of research publications from Prof. Hölscher’s groupA list of research publications from Prof. Hölscher’s group
(Manuscripts can be found on Researchgate free of charge)
Full papers (reviews are further down)
Paul Edison, Grazia Femminella, Craig Ritchie, Clive Holmes, Joseph Nowell, Zuzana Walker, Basil Ridha, Sanara Raza, Nicholas R. Livingston, Gail Busza, Eleni Frangou, Sharon Love, Gareth Williams, Robert Lawrence, Brady Mcfarlane, Hilary Archer, Elizabeth Coulthard, Benjamin R Underwood, Paul Koranteng, Salman Karim, Carol Bannister, Robert Perneczky, Aparna Prasanna, Kehinde Junaid, Bernadette McGuinness, Ramin Nilforooshan, Ajay Macharouthu, Andrew Donaldson, Simon Thacker, Gregor Russell, Nagma Malik, Vandana Mate, Lucy Knight, Sajeev Kshemendran, Christian Holscher, Anita Mansouri, Mae Chester-Jones, Jane Holmes, Trisha Tan, Steve Williams, David J Brooks, John Harrison, Rainer Hinz, George Tadros, Anthony Peter Passmore, Clive Ballard (2023): Evaluation of Liraglutide as a Treatment for Alzheimer’s disease: The ELAD Randomized Clinical Trial. The Lancet, submitted.
Zijuan Zhang,·Ziyang Yu,·Ye Yuan,·Jing Yang,·Shijie Wang,·He Ma,·Li Hao,·Jinlian Ma,·Zhonghua Li,·Zhenqiang Zhang,·Christian Hölscher (2023): Cholecystokinin signaling can rescue cognition and synaptic plasticity in the APP/PS1 mouse model of Alzheimer’s disease. Molecular Neurobiology, DOI:10.1007/s12035-023-03388-7. https://rdcu.be/ddhMF
Hong-Yan Cai, Si-Ru Chen, Yu Wang, Juan-Juan Jiao, Jun Qiao, Christian Hölscher, Zhao-Jun Wang, Sheng-Xiao Zhang, Mei-Na Wu (2023): Integrated analysis of the lncRNA-associated ceRNA network in Alzheimer’s disease. Gene, 876:147484. https://www.sciencedirect.com/science/article/pii/S0378111923003256
Lingyu Zhang, Chun Li, Zijuan Zhang, Zhenqiang Zhang, Qian-Qian Jin, Lin Li, Christian Hölscher (2022): DA5-CH and Semaglutide protect against neurodegeneration and reduce α-synuclein levels in the 6-OHDA Parkinson’s disease rat model. Parkinson’s Disease, https://www.hindawi.com/journals/pd/2022/1428817/
Yunfang Su, Ningning Liu, Zijuan Zhang, Li Hao, Jinlian Ma, Ye Yuan, Ming Shi, Jihong Liu, Zhenrong Zhao, Zhenqiang Zhang, Christian Holscher (2022): Cholecystokinin and glucagon-like peptide-1 analogues regulate intestinal tight junction, inflammation, dopaminergic neurons and α-synuclein accumulation in the colon of two Parkinson`s disease mouse models. Eur J Pharmacol., 926:175029, https://doi.org/10.1016/j.ejphar.2022.175029
Hong-Yan Cai, Jing Qiao, Si-Ru Chen, Jun-Ting Yang, Christian Hölscher, Zhao-Jun Wang, Jin-Shun Qi, Mei-Na Wu (2022): MCU-knockdown in hippocampal neurons improves memory performance in the APP/PS1/tau transgenic mouse model of Alzheimer’s disease. Acta Biochimica et Biophysica Sinica, 54(10):1–12.
Zijuan Zhang, Li Hao, Yunfang Su, Jinlian Ma, Ye Yuan, Ziyang Yu, Ming Shi, Simai Shao, Zhenqiang Zhang, Christian Hölscher (2022): Neuroprotective Effects of a Cholecystokinin Analogue in the MPTP Parkinson’s Disease Mouse Model. Frontiers in Neuroscience, 16:814430. DOI:10.3389/fneur.2022.844697
Guang-Zhao Yang, Qi-Chao Gao, Wei-Ran Li, Hong-Yan Cai, Hui-Min Zhao, Jian-Ji Wang, Xin-Rui Zhao, Jia-Xin Wang, Mei-Na Wu, Jun Zhang, Christian Hölscher, Jin-Shun Qi, Zhao-Jun Wang (2022): (D-Ser2) oxyntomodulin recovers hippocampal synaptic function and theta rhythm in Alzheimer’s disease transgenic mice. Neural Regen Res, 17:2072-2078.
Edison P., Femminella, G. D., E. Frangou, S. B. Love, G. Busza, C. Holmes, C. Ritchie, R. Lawrence, B. McFarlane, G. Tadros, B. H. Ridha, C. Bannister, Z. Walker, H. Archer, E. Coulthard, B. R. Underwood, A. Prasanna, P. Koranteng, S. Karim, K. Junaid, B. McGuinness, R. Nilforooshan, A. Macharouthu, A. Donaldson, S. Thacker, G. Russell, N. Malik, V. Mate, L. Knight, S. Kshemendran, J. Harrison, C. Hölscher, D. J. Brooks, A. P. Passmore, C. Ballard (2021) Evaluation of liraglutide in the treatment of Alzheimer’s disease. Alzheimer & Dementia 17:S9.
Hong-Yan Cai, Dan Yang, Jing Qiao, Jun-Ting Yang, Zhao-Jun Wang, Mei-Na Wu, Jin-Shun Qi, Christian Hölscher (2021): A GLP-1/GIP dual receptor agonist DA4-JC effectively attenuates cognitive impairment and pathology in the APP/PS1/tau model of Alzheimer’s disease. J Alzheimer Dis, 83(2):799-818.
Keerie A, Brown-Wright H, Kirkland I, Grierson A, Alix JJP, Holscher C, Mead RJ. (2021): The GLP-1 receptor agonist, liraglutide, fails to slow disease progression in SOD1G93A and TDP-43Q331K transgenic mouse models of ALS. Sci Rep. 11(1):17027.
MiaoJun Lv, GuoFang Xue, HuiFeng Cheng, PengFei Meng, Xia Lian, Christian Hölscher, DongFang Li (2021): The GLP-1/GIP dual-receptor agonist DA5-CH inhibits the NF-κB inflammatory pathway in the MPTP mouse model of Parkinson’s disease more effectively than the GLP-1 single-receptor agonist NLY01. Brain and Behavior, 75(3):540-552. DOI:https://doi.org/10.1002/brb3.2231
G, Xie Z, Li EW, Yuan Y, Fu Y, Wang P, Zhang X, Qiao Y, Xu J, Holscher C, Wang H, Zhang Z (2021) Dehydroabietic acid improves nonalcoholic fatty liver disease through activating the Keap1/Nrf2-ARE signaling pathway to reduce ferroptosis. J Nat Med. DOI:10.1007/s11418-021-01491-4
Femminella GD, Livingston NR, Raza S, van der Doef T, Frangou E, Love S, Busza G, Calsolaro V, Carver S, Holmes C, Ritchie CW, Lawrence RM, McFarlane B, Tadros G, Ridha BH, Bannister C, Walker Z, Archer H, Coulthard E, Underwood B, Prasanna A, Koranteng P, Karim S, Junaid K, McGuinness B, Passmore AP, Nilforooshan R, Macharouthu A, Donaldson A, Thacker S, Russell G, Malik N, Mate V, Knight L, Kshemendran S, Tan T, Holscher C, Harrison J, Brooks DJ, Ballard C, Edison P. (2021): Does insulin resistance influence neurodegeneration in non-diabetic Alzheimer’s subjects? Alzheimer’s Res Ther, 13:47. DOI: 10.1186/s13195-021-00784-w.
Li Yuan, Jun Zhang, Jun-Hong Guo, Christian Holscher, Jun-Ting Yang, Mei-Na Wu, Zhao-Jun Wang, Hong-Yan Cai, Ling-Na Han, Hui Shi, Yu-Fei Han, Jin-Shun Qi (2021): DAla2-GIP-GLU-PAL Protects Against Cognitive Deficits and Pathology in APP/PS1 Mice by Inhibiting Neuroinflammation and Upregulating cAMP/PKA/CREB Signaling Pathways. J Alzheimer Dis, DOI:10.1007/s11418-021-01491-4.
Zijuan Zhang, Li Hao, Ming Shi, Ziyang Yu, Simai Shao, Ye Yuan, Zhenqiang Zhang, Christian Hölscher (2021): Neuroprotective effects of a GLP-2 analogue in the MPTP Parkinson’s disease mouse model. J Parkinson Dis, DOI:10.3233/JPD-202318.
Yunfang Su, Zijuan Zhang, Li Hao, Jinlian Ma, Limin Sun, Simai Shao, Zhenqiang Zhang, Christian Holscher (2021): GLP-2 agonist protects SH-SY5Y and Neuro-2a cells against mitochondrial damage, autophagy impairments and apoptosis in a Parkinson model. Drug Research, 71:43-50.
Bo Bai, DongFang Li, GuoFang Xue, Peng Feng, MeiQin Wang, YuDi Han, YaNan Wang, Christian Hölscher (2021): The novel GLP-1 / GIP dual agonist DA3-CH is more effective than liraglutide in reducing endoplasmic reticulum stress in diabetic rats with cerebral ischemia-reperfusion injury. Nutrition, Metabolism and Cardiovascular Diseases, 31:333-343.
Also worth reading:
Salameh TS, Rhea EM, Talbot K, Banks WA (2020): Brain uptake pharmacokinetics of incretin receptor agonists showing promise as Alzheimer’s and Parkinson’s disease therapeutics. Biochemical Pharmacology, 180:114187.
Correction to (author addition): Femminella, G. D., E. Frangou, S. B. Love, G. Busza, C. Holmes, C. Ritchie, R. Lawrence, B. McFarlane, G. Tadros, B. H. Ridha, C. Bannister, Z. Walker, H. Archer, E. Coulthard, B. R. Underwood, A. Prasanna, P. Koranteng, S. Karim, K. Junaid, B. McGuinness, R. Nilforooshan, A. Macharouthu, A. Donaldson, S. Thacker, G. Russell, N. Malik, V. Mate, L. Knight, S. Kshemendran, J. Harrison, C. Hölscher, D. J. Brooks, A. P. Passmore, C. Ballard, and P. Edison (2020) :”Evaluating the effects of the novel GLP-1 analogue liraglutide in Alzheimer’s disease: study protocol for a randomised controlled trial (ELAD study).” Trials, DOI: 10.1186/s13063-020-04608-4
Ling-Yu Zhang, Qian-Qian Jin, Lin Li, Christian Hölscher (2021): The GLP-1/GIP dual receptor agonist DA5-CH is superior to Exendin-4 in protecting neurons in the 6-OHDA rat Parkinson Model. Neural Regeneration Research, 16:1660-1670.
Mark Maskery, Elizabeth Mary Goulding, Simon Gengler, Josefine Ulrikke Melchiorsen, Mette Marie Rosenkilde, Christian Hölscher (2020): The dual GLP-1/GIP receptor agonist DA4-JC shows superior protective properties compared to the GLP-1 analogue liraglutide in the APP/PS1 mouse model of Alzheimer’s disease. American Journal of Alzheimer’s disease & other dementias, 35:1533317520953041. DOI: 10.1177/1533317520953041.
Zhishen Xie, Gai Gao, Hui Wang, Erwen Li, Young Yuan, Yu Fu, Junying Song, Christian Hölscher, Jiangyan Xu, Zhenqiang Zhang (2020): Dehydroabietic acid prevents high fat diet-induced insulin resistance and hepatic steatosisinvolve PPAR-γ and PPAR-α. Biomedicine and Pharmacotherapy, 127:110155.
Li, T., L. Tu, R. Gu, X. L. Yang, X. J. Liu, G. P. Zhang, Q. Wang, Y. P. Ren, B. J. Wang, and J. Y. Tian. (2020): Neuroprotection of GLP-1/GIP receptor agonist via inhibition of mitochondrial stress by AKT/JNK pathway in a Parkinson’s disease model. Life Sci: 117824. https://doi.org/10.1016/j.lfs.2020.117824.
Tian Li, Juan-Juan Jiao, Qiang Su, Christian Hölscher, Jun Zhang, Xu-Dong Yan, Hui-Min Zhao, Hong-Yan Cai, and Jin-Shun Qi (2020): A GLP-1/GIP/Gcg receptor triagonist alleviates memory impairments in 3xTg-AD mice via improving synaptic transmission, neuronal excitability and Ca2+ homeostasis. Neuropharmacology, 170:108042.
Zhang Zijuan, Jing Ying, Duan Dongxiao, Li Bo, Hölscher Christian, Li Cheng, Wei Jingwen, Gao Aishe, Shang Lizhi, Tao Feng, Xing Yinga (2020): Driving GABAergic neurons optogenetically improves learning, reduces amyloid load and enhances autophagy in a mouse model of Alzheimer’s disease. Biochemical and Biophysical Research Communications, 525:928-935.
Wang ZJ, Han YF, Zhao F, Yang GZ, Yuan L, Cai HY, Yang JT, Holscher C, Qi JS, Wu MN (2020): A dual GLP-1 and Gcg receptor agonist rescues spatial memory and synaptic plasticity in APP/PS1 transgenic mice. Hormones and Behavior, DOI:10.1016/j.yhbeh.2019.104640
Lingyu Zhang, Liping Zhang, Yanwei Li, Lin Li, Josefine Ulrikke Melchiorsen, Mette Rosenkilde, Christian Hölscher (2020): The novel dual GLP-1/GIP receptor agonist DA-CH5 is superior to single GLP-1 receptor agonists in the MPTP model of Parkinson’s disease. J Parkinson Dis, 10:523-542. DOI:10.3233/JPD-191768.
Zhishen Xie, Jianping Zhao, Hui Wang, Yali Jiang, Qiaoling Yang, Yu Fu, Huahui Zeng, Christian Hölscher, Jiangyan Xu, Zhenqiang Zhang (2020): Magnolol alleviates Alzheimer’s disease-like pathology in transgenic C. elegans by promoting microglia phagocytosis and the degradation of beta-amyloid through activation of PPAR-γ. Biomedicine & Pharmacotherapy 124:109886
Femminella, G. D., E. Frangou, S. B. Love, G. Busza, C. Holmes, C. Ritchie, R. Lawrence, B. McFarlane, G. Tadros, B. H. Ridha, C. Bannister, Z. Walker, H. Archer, E. Coulthard, B. R. Underwood, A. Prasanna, P. Koranteng, S. Karim, K. Junaid, B. McGuinness, R. Nilforooshan, A. Macharouthu, A. Donaldson, S. Thacker, G. Russell, N. Malik, V. Mate, L. Knight, S. Kshemendran, J. Harrison, C. Hölscher, D. J. Brooks, A. P. Passmore, C. Ballard, and P. Edison (2019): Evaluating the effects of the novel GLP-1 analogue liraglutide in Alzheimer’s disease: study protocol for a randomised controlled trial (ELAD study). Trials20 (1): 191. https://doi.org/10.1186/s13063-019-3259-x
Cheng Li, Weizhen Liu, Xiaohui Li, Zijuan Zhang, Huaxin Qi, Shijin Liu, Ningning Yan, Ying Xing, Christian Hölscher, Zhiju Wang (2019): The novel GLP-1/GIP Analogue DA5-CH reduces tau phosphorylation and normalizes theta rhythm in the icv. STZ rat model of AD. Brain and Behavior, 10:e01505. DOI:10.1002/brb3.1505.
Salles GN, Calió ML, Hölscher C, Pacheco-Soares C, Porcionatto M, Lobo AO (2019): Neuroprotective and restorative properties of the GLP-1/GIP dual agonist DA-JC1 compared with a GLP-1 single agonist in Alzheimer’s disease. Neuropharmacology, 162:107813.
Xiaoyan Yang, Peng Feng, Xiangjian Zhang, Dongfang Li, Ruifang Wang, Chenhui Ji, Guanglai Li, Christian Hölscher (2019): The diabetes drug semaglutide reduces infarct size, inflammation, and apoptosis, and normalizes neurogenesis in a rat model of stroke. Neuropharmacology, 158:107748.
Wang L, Zhao J, Wang CT, Hou XH, Ning N, Sun C, Guo S, Yuan Y, Li L, Hölscher C, Wang XH (2019): D-Ser2-oxyntomodulin ameliorated Aβ31-35-induced circadian rhythm disorder in mice. CNS Neurosci Ther. doi: 10.1111/cns.13211.
Miao-Jing Tian, Rui-Fang Wang, Christian Hölscher, Ru-Lin Mi, Zhen-Yu Yuan, Dong-Fang Li, Guo-Fang Xue (2019): The novel GLP-1/GIP dual receptor agonist DA3-CH is neuroprotective in the pilocarpine-induced epileptogenesis rat model. Epilepsy Research, 154:97-106.
Li Wang, Rui Zhang, Xiaohong Hou, Changtu Wang, Shuai Guo, Na Ning, Cong Sun, Yuan Yuan, Lin Li, Christian Hölscher and Xiaohui Wang (2019): DA-JC1 improves learning and memory by antagonizing Aβ31–35-induced circadian rhythm disorder. Molecular Brain 12:1-14.
Liping Zhang, LingYu Zhang, Lin Li, Christian Hölscher (2019): Semaglutide is neuroprotective and reduces alpha-synuclein levels in the chronic MPTP mouse model of Parkinson’s disease. Journal of Parkinson’s Disease, 9:157-171.
Holubová M., Hruba L., Popelová A., Bencze M., Pražienková V., Gengler S., Kratochvílová H., Haluzik M., Zelezná B., Kuneš J., Hölscher C., Maletínská L. (2018): Liraglutide and a lipidized analog of prolactin-releasing peptide show neuroprotective effects in a mouse model of β-amyloid pathology. Neuropharmacology, 144:377-387.
Muhammad L. Nasaruddin, Xiaobei Pan, Bernadette McGuinness, Peter Passmore, Patrick G. Kehoe, Christian Hölscher, Stewart F. Graham and Brian D. Green (2018): Evidence That Parietal Lobe Fatty Acids May Be More Profoundly Affected in Moderate Alzheimer’s Disease (AD) Pathology Than in Severe AD Pathology. Metabolites 2018, 8, E69.
Salles GN, Calió ML, Afewerki S, Pacheco-Soares C, Porcionatto M, Hölscher C, Lobo AO. (2018): Prolonged Drug-Releasing Fibers Attenuate Alzheimer’s Disease-like Pathogenesis. ACS Appl Mater Interfaces, 10:36693-36702.
Theodora Panagaki, Simon Gengler and Christian Hölscher (2018): The novel DA-CH3 dual incretin restores ER stress and autophagy impairments to attenuate Alzheimer’s-like pathology and cognitive decrements in the APPswe/PS1ΔE9 mouse model. J Alzheimer Disease,66:195-218.
Liping Zhang, Lingyu Zhang, Lin Li, Christian Hölscher (2018): Neuroprotective effects of the novel GLP-1 long acting analogue semaglutide in the MPTP Parkinson’s disease mouse model. Neuropeptides, 71:70-80.
Han Weina, Niu Yuhu, Holscher Christian, Li Birong, Shen Feiyu, Wang Le (2018): Liraglutide Attenuates the Depressive- and Anxiety-like Behaviour in the Corticosterone Induced Depression Model Via Improving Hippocampal Neural Plasticity. Brain Res, 1694:55-62.
Yue Cao, Christian Hölscher, Meng-Ming Hu, Ting Wang, Fang Zhao, Yu BAI, Jun Zhang, Mei-Na Wu, Jin-Shun Qi (2018): DA5-CH, A Novel GLP-1/GIP Dual Agonist, Effectively Ameliorates Cognitive Impairments and Pathology in the APP/PS1 Mouse Model of Alzheimer’s Disease. Eur J Pharmacol, 827:215-226.
Rui-Fang Wang, Guo-Fang Xue, Christian Hölscher, Miao-Jing Tian, Peng Feng, Ji-Ying Zheng and Dong-Fang Li (2018): Post-treatment with the GLP-1 analogue liraglutide alleviate chronic inflammation and mitochondrial stress induced by Status epilepticus. Epilepsy Research, 142:45-62.
Tian Li, Juan-Juan Jiao, Christian Hölscher, Mei-Na Wu, Jun Zhang, Jia-Qing Tong, Xue-Fan Dong, Xue-Song Qu, Yue Cao, Hong-Yan Cai, Jin-Shun Qi (2018): A Novel GLP-1/GIP/Gcg Triagonist Reduces Cognitive Deficits and Pathology in the 3xTg Mouse Model of Alzheimer’s Disease. Hippocampus, 28:358-372.
Peng Feng, Xiangjian Zhang, Dongfang Li, Chenhui Ji, Ziyue Yuan, Ruifang Wang, Guofang Xue, Guanglai Li, Christian Hölscher (2018): Two novel dual GLP-1/GIP receptor agonists are neuroprotective in the MPTP mouse model of Parkinson’s disease. Neuropharmacology, 133:385-394.
Andre F. Batista, Leticia Forny-Germano, Julia R. Clarke, Natalia M. Lyra e Silva, Jordano Brito-Moreira1, Susan E. Boehnke, Andrew Winterborn, Brian C. Coe, Ann Lablans, Juliana F. Vital, Suelen A. Marques, Ana M. B Martinez, Matthias Gralle, Christian Holscher, William L. Klein, Jean-Christophe Houzel, Sergio T. Ferreira, Douglas P. Munoz and Fernanda G. De Felice (2018): The diabetes drug liraglutide reverses cognitive impairment in mice and attenuates insulin receptor and synaptic pathology in a non-human primate model of Alzheimer’s disease. Journal of Pathology, 245:85-100.
Panagaki T., Michael M., Hölscher C. (2017): Liraglutide restores chronic ER stress, autophagy impairments and apoptotic signalling in SH-SY5Y cells. Scientific Reports, 7:16158pp, DOI:10.1038/s41598-017-16488-x
Jingjing Tai, Weizhen Liu, Yanwei Li, Lin Li, Christian Hölscher (2018): Neuroprotective effects of a Triple GLP-1/GIP/Glucagon receptor agonist in the APP/PS1 transgenic mouse model of Alzheimer’s disease. Brain Res, 1678:64-74.
Ziyue Yuan, Dongfang Li, Peng Feng, Guofang Xue, Chenhui Ji, Guanglai Li, Christian Hölscher (2017): A novel GLP-1/GIP dual agonist is more effective than liraglutide in reducing inflammation and enhancing GDNF release in the MPTP mouse model of Parkinson’s disease. Eur J Pharmacol., 812:82-90.
Qian-qian Jin, Jun-hong Sun, Qiu-xiang Du, Xiao-jun Lu, Xi-yan Zhu, Hao-liang Fan, Christian Hölscher,Ying-yuan Wang (2017): Integrating microRNA and mRNA expression profiles in a rat model of deep vein thrombosis. International Journal of Molecular Medicine, 40(4):1019-1028.
Xiaobei Pan, Chris Elliott, Bernadette McGuiness, Peter Passmore, Patrick Kehoe, Christian Hölscher, Paula McClean, Stewart Graham, Brian Green (2017): Metabolomic profiling of bile acids in clinical and experimental samples of Alzheimer’s disease. Metabolites, 7(28):1-13.
Lijuan Shi, Zhihua Zhang, Lin Li, Christian Hölscher (2017): A novel dual GLP-1 / GIP receptor agonist alleviates cognitive decline by re-sensitizing insulin signaling in the Alzheimer icv. STZ rat model. Behav. Brain Res., 237:65-74.
Jaishree Jalewa, Mohit Kumar Sharma, Simon Gengler and Christian Hölscher (2017): A novel GLP-1/GIP dual receptor agonist protects from 6-OHDA lesion in a rat model of Parkinson’s disease. Neuropharmaology, 117:238-248.
Yanwei Li, WeiZhen Liu, Lin Li, Christian Hölscher (2017): D-Ala2-GIP-glu-PAL is neuroprotective in a chronic Parkinson’s disease mouse model and increases BNDF expression while reducing neuroinflammation and lipid peroxidation. Eur J Pharmacol, 797:162-172.
Hong-Yan Cai, Zhao-Jun Wang, Christian Hölscher, Li Yuan, Jun Zhang, Peng Sun, Jing Li, Wei Yang, Mei-Na Wu, Jin-Shun Qi (1917): Lixisenatide Attenuates the Detrimental Effects of β-Amyloid on Spatial Working Memory and Cultured Hippocampal Neurons of Rats. Behav Brain Res, 318:28-35.
Ji, C., Xue, G. F., Lijun, C., Feng, P., Li, D., Li, L., Li, G., Holscher, C., (2016): A novel dual GLP-1 and GIP receptor agonist is neuroprotective in the MPTP mouse model of Parkinson’s disease by increasing expression of BNDF. Brain Res 1634, 1-11.
Geisa Nogueira Salles, Fernanda Aparecida dos Santos Pereira, Cristina Pacheco-Soares, Fernanda Roberta Marciano, Christian Hölscher, Thomas Jay Webster, Anderson de Oliveira Lobo (2016): A novel bioresorbable ultrathin device as a controlled release system for protecting cells from oxidative stress from Alzheimer’s disease. Molecular Neurobiology, DOI: 10.1007/s12035-016-0200-0.
Yan Du, Li Du, Jie Cao，Christian Hölscher，Yongming Feng，Hongliang Su, Yujin Wang, Ke-Ming Yun (2017): Levo-tetrahydropalmatine inhibits the acquisition of ketamine-induced conditioned place preference by regulating the expression of ERK and CREB phosphorylation in rats. Behav Brain Res., 317:367-373.
Jaishree Jalewa, Mohit Kumar Sharma and Christian Hölscher (2016): Novel Incretin analogues improve autophagy and protect from mitochondrial stress induced by rotenone in SH-SY5Y cells. J Neurochem., 139(1):55-67.
Nasaruddin ML, Hölscher C, Kehoe P, Graham SF, Green BD (2016): Wide-ranging alterations in the brain fatty acid complement of subjects with late Alzheimer’s disease as detected by GC-MS. Am J Transl Res, 8:154-65.
Lin Li, Ke Liu, Juan Zhao, Christian Hölscher, Guang-lai Li, Yue-ze Liu (2016): Neuroprotective role of (Val8)GLP-1-Glu-PAL in an in vitro model of Parkinson’s disease. Neural Regen Res, 11:326-331.
Lijun Cao, Dongfang Li, Peng Feng, Lin Li, Guo-Fang Xue, Guanglai Li, Christian Hölscher (2016): A novel dual GLP-1 and GIP incretin receptor agonist is neuroprotective in a mouse model of Parkinson’s disease by reducing chronic inflammation in the brain. Neuroreport, 37:384-391.
Adrian Olmos-Alonso, Sjoerd T.T. Schetters, Sarmi Sri, Katharine Askew, Renzo Mancuso, Mariana Vargas-Caballero, Christian Hölscher, V. Hugh Perry, Diego Gomez-Nicola (2016): Pharmacological targeting of CSF1R inhibits microglial proliferation and prevents the progression of Alzheimer’s-like pathology. Brain, 139:891-907.
Xiaobei Pan; Muhammad L Nasaruddin; Christopher T Elliott; Bernadette McGuinness; Peter Passmore; Patrick G Kehoe; Christian Hölscher; Paula L McClean; Stewart F Graham; Dr. Brian Green (2016): Alzheimer’s disease-like pathology has transient effects on the brain and blood metabolome. Neurobiology of Aging, 38:151-163.
Yanwei Li, WeiZhen Liu, Lin Li, Christian Hölscher (2015): Neuroprotective effects of a GIP analogue in the MPTP Parkinson’s disease mouse model. Neuropharmacol, 101:255-263.
Han, Ling, Hölscher, Christian, Xue, Guo-Fang, Li, Guanglai, Li, Dongfang, (2015): A novel dual Glucagon-Like Peptide-1 and Glugose-dependent Insulinotropic Polypeptide receptor agonist is neuroprotective in transient focal cerebral ischaemia in the rat. Neuroreport, 27:23-32.
Chenhui Ji, Guo-Fang Xue, Cao Lijun, Peng Feng, Dongfang Li, Lin Li, Guanglai Li, Christian Hölscher (2015): A novel dual GLP-1 and GIP receptor agonist is neuroprotective in the MPTP mouse model of Parkinson’s disease by increasing expression of BNDF. Brain Res, 1634:1-11.
YiMei Chen, Yanfang Zhang, Lin Li, Christian Hölscher (2015): Neuroprotective effects of geniposide in the MPTP mouse model of Parkinson’s disease. Eur J Pharmacol, 768:21-27.
WeiZhen Liu, Yanwei Li, Jaishree Jalewa, Taylor Saunders-Wood, Lin Li, Christian Hölscher (2015): Neuroprotective effects of an oxyntomodulin analogue in the MPTP mouse model of Parkinson’s disease. Eur J Pharmacol, 765:284-290.
Paula L McClean, Jaishree Jalewa and Christian Hölscher (2015): Prophylactic liraglutide treatment prevents amyloid plaque deposition, chronic inflammation and memory impairment in APP/PS1 mice. Behav Brain Res, 293:96-106.
YanFang Zhang, YiMei Chen, Lin Li, Christian Hölscher (2015): Neuroprotective effects of (Val8)GLP-1-Glu-PAL in the MPTP Parkinson’s disease mouse model. Behav Brain Res, 293:107-113.
WeiZhen Liu, Jaishree Jalewa, Mohit Sharma, Guanglai Li, Lin Li, Christian Hölscher (2015): Neuroprotective effects of lixisenatide and liraglutide in the MPTP mouse model of Parkinson’s disease. Neuroscience, 303:42-50. DOI:10.1016/j.neuroscience.2015.06.054
Stewart F. Graham, Christian Hölscher, Bernadette McGuinness, Patrick G. Kehoe, Seth Love, Peter Passmore, Christopher T. Elliott, Andrew A. Meharg and Brian D. Green (2015): Untargeted metabolomic analysis of human plasma indicates differentially affected polyamine and L-arginine metabolism in Mild Cognitive Impairment subjects converting to Alzheimer’s disease. PLoS ONE 10(3): e0119452. doi:10.1371/journal.pone.0119452.
Ryo Ohshima, Kanae Hotsumi, Christian Hölscher, Kenjiro Seki (2015): Age-Related Decrease in Glucagon-Like Peptide-1 in Mouse Prefrontal Cortex but Not in Hippocampus Despite the Preservation of Its Receptor. American Journal of BioScience, 3(1): 11-27. Doi: 10.11648/j.ajbio.20150301.13
Patricia Kelly, Paula McClean, Maximilian Ackermann, Moritz A. Konerding, Christian Hölscher and Christopher A. Mitchell (2015): Restoration of cerebral and systemic microvascular architecture in APP/PS1 transgenic mice following treatment with Liraglutide. Microcirculation, 22:133-145.
McClean, PL and Holscher, C (2014): Lixisenatide, a drug developed to treat type 2 diabetes, shows neuroprotective effects in a mouse model of Alzheimer ‘s disease. Neuropharmacol. 86:241-258.
Stewart F. Graham, Muhammad Bin Nasaruddin, Manus Carey, Christian Holscher, Bernadette McGuinness, Patrick G. Kehoe, Seth Love, Peter Passmore, Christopher T. Elliott, Andrew A. Meharg and Brian D. Green (2014): Age-associated changes of brain copper, iron and zinc in Alzheimer’s disease and Lewy body dementia. Journal of Alzheimer’s Disease, 42:1407-1413.
Lennox R, Porter DW, Flatt PR, Holscher C, Irwin N, Gault, VA (2014): Comparison of the independent and combined effects of sub-chronic therapy with metformin and a stable GLP-1 receptor agonist on cognitive function, hippocampal synaptic plasticity and metabolic control in high-fat fed mice. Neuropharmacology, 88C:23-30.
Stewart F. Graham, Muhammad Bin Nasaruddin, Manus Carey, Christian Holscher Bernadette McGuinness, Patrick G. Kehoe, Seth Love, Peter Passmore, Christopher T. Elliott, Andrew A. Meharg and Brian D. Green (2014): Age-associated changes of brain copper, iron and zinc in Alzheimer’s disease and Lewy body dementia. Journal of Alzheimer’s Disease, 42:1407-1413.
Jaishree Jalewa; Wong-Lin KongFatt, Martin McGinnity, Girijesh Prasad, Christian Holscher (2014): Increased number of orexin/hypocretin neurons with high and prolonged external stress-induced depression. Behav Brain Res, 272:196-274.
Hong-Yan Cai, Christian Hölscher, Xing-Hua Yue, Sheng-Xiao Zhang, Xiao-Hui Wang, Feng Qiao, Wei Yang, Jin-Shun Qi (2014): Lixisenatide rescues spatial memory and synaptic plasticity from amyloid β protein-induced impairments in rats. Neuroscience, 277C:6-13.
Jaishree Jalewa, Alok Joshi, T. Martin McGinnity, Girijesh Prasad, KongFatt Wong-Lin, Christian Hölscher (2014): Neural Circuit Interactions between the Dorsal Raphe Nucleus and the Lateral Hypothalamus: An Experimental and Computational Study. PLOS One, vol. 9, issue 2, p88003
Mychael V. Lourenço, Julia R. Clarke, Rudimar L. Frozza, Theresa R. Bomfim, Letícia Forny-Germano, André F. Batista, Luciana B. Sathler, Jordano Brito-Moreira, Olavo B. Amaral, Cesar A. Silva, Léo Freitas-Correa, Sheila Espírito-Santo, Paula Campello-Costa, Jean-Christophe Houzel, William L. Klein, Christian Holscher, José B. Carvalheira, Aristobolo M. Silva, Lício A. Velloso, Douglas P. Munoz, Sergio T. Ferreira, Fernanda G. De Felice. (2013): TNF-a mediates brain IRS-1 inhibition and PKR-dependent memory impairment induced by Alzheimer’s linked amyloid-ß oligomers in mice and monkeys. Cell Metabolism, 18(6):831-843.
Paula L McClean and Christian Hölscher (2014): Liraglutide can reverse memory impairment, synaptic loss and reduce plaque load in aged APP/PS1 mice, a model of Alzheimer ‘s disease. Neuropharmacol., 76:57-67.
Mohit Kumar Sharma, Jaishree Jalewa, and Christian Hölscher (2013): Neuroprotective and anti-apoptotic effects of Liraglutide on SH-SY5Y cells exposed to Methylglyoxal stress. J Neurochem, 128:459-471.
Parthsarathy V. and Hölscher C (2013): Chronic treatment with the GLP1 analogue liraglutide increases cell proliferation and differentiation into neurons in an AD mouse model. PLoS ONE, 8(3):e58784. doi: 10.1371/journal.pone.0058784
Emilie Faivre and Christian Hölscher (2013): Neuroprotective effects of D-Ala2GIP on Alzheimer’s disease biomarkers in an APP/PS1 mouse model. Alzheimers Res Ther, 5:20-29.
Emilie Faivre and Christian Hölscher (2013): D-Ala2GIP facilitated synaptic plasticity and reduces plaque load in aged wild type mice and in an Alzheimer’s disease mouse model. J Alzheimer’s Disease, 35:267-283.
Parthsarathy V, McClean PL, Hölscher C, Taylor M, Tinker C, Jones G, Kolosov O, Salvati E, Gregori M, Masserini M, Allsop D. (2013): A Novel Retro-Inverso Peptide Inhibitor Reduces Amyloid Deposition, Oxidation and Inflammation and Stimulates Neurogenesis in the APPswe/PS1ΔE9 Mouse Model of Alzheimer’s Disease. PLoS One. 2013;8(1):e54769. doi: 10.1371/journal.pone.0054769.
Aisling M Duffy and Christian Hölscher (2013): The incretin analogue D-Ala2GIP reduces plaque load, astrogliosis and oxidative stress in an APP/PS1 mouse model of Alzheimer’s disease. Neuroscience, 228:294-300.
Wei-Na Han, Christian Holscher, Li Yuan, Wei Yang, Xiao-hui Wang, Mei-Na Wu, Jin-Shun Qi (2013): Liraglutide protects against ß-amyloid induced impairment of spatial learning and memory in rats. Neurobiol Aging, 34:576-588.
Graham SF, Chevallier OP, Roberts D, Holscher C, Elliott CT, Green BD (2013): An investigation of the human brain metabolome to identify potential markers for early diagnosis and therapeutic targets of Alzheimer’s Disease. Analytical Chemistry, 85:1803-11.
Parthsarathy V., Holscher C (2013): The type 2 diabetes drug Liraglutide reduces chronic inflammation induced by irradiation in the mouse brain. Eur J Pharmacol. 700:42-50.
Stewart Graham, Christian Holscher, Paula McClean, Christopher Elliott, Brian Green (2013): 1H NMR metabolomics investigation of an Alzheimer’s disease (AD) mouse model pinpoints important biochemical disturbances in brain and plasma. Metabolomics, 9:974-983.
Xiao-Hui Wang, Wei Yang, Christian Hölscher, Zhao-Jun Wang, Hong-Yan Cai, Qing-Shan Li, Jin-Shun Qi (2013): Val8-GLP-1 Remodels Synaptic Activity and Intracellular Calcium Homeostasis Impaired by Amyloid β Peptide in Rats, J Neurosci Res, 91:568-77.
Han WN, Hölscher C, Yuan L, Yang W, Wang XH, Wu MN, Qi JS. (2013): Liraglutide protects against amyloid-β protein-induced impairment of spatial learning and memory in rats. Neurobiol Aging. 2013 Feb;34(2):576-88.
Long-Smith CM, Manning S, McClean PL, Coakley MF, O’Halloran DJ, Holscher C, O’Neill C. (2013): The Diabetes Drug Liraglutide Ameliorates Aberrant Insulin Receptor Localisation and Signalling in Parallel with Decreasing Both Amyloid-β Plaque and Glial Pathology in a Mouse Model of Alzheimer’s Disease. Neuromolecular Med. 15:102-114.
McGovern, S, Hunter K, Holscher C (2012): Effects of the Glucagon-Like Polypeptide-1 analogue (Val8)GLP-1 on learning, progenitor cell proliferation and neurogenesis in the C57B/16 mouse brain. Brain Res. 1473:204-213.
Porter D., Peter R Flatt, Christian Hölscher and Victor A Gault (2012): Liraglutide improves hippocampal synaptic plasticity associated with increased expression of Mash1 in ob/ob mice. Int J Obesity, DOI: 10.1038/ijo.2012.91
Hunter K., Holscher C. (2012): Drugs developed to treat diabetes, liraglutide and lixisenatide, cross the blood brain barrier and enhance neurogenesis. BMC Neuroscience, 13:33-38.
Hamilton A., Holscher C. (2012): The effect of aging on neurogenesis and oxidative stress in the APP/PS1deltaE9 mouse model of Alzheimer’s disease. Brain Res., 1449:83-93.
Porter D, Faivre E, Flatt PR, Hölscher C, Gault VA. (2012): Actions of incretin metabolites on locomotor activity, cognitive function and in vivo hippocampal synaptic plasticity in high fat fed mice. Peptides 35:1-8.
Theresa R. Bomfim, Leticia Forny-Germano, Luciana B. Sathler, Jordano Brito-Moreira, Jean Christophe-Houzel, Helena Decker, Michael A. Silverman, Paula L. McClean, Christian Holscher, Hala Kazi, Steven E. Arnold, Konrad Talbot, William L. Klein, Douglas P. Munoz, Sergio T. Ferreira and Fernanda G. De Felice (2012): IRS-1 inhibition links impaired insulin signaling in Alzheimer’s andtype-2 diabetes: Protection by anti-diabetic drugs. J Clin Invest, 122:1339-53
Gengler S, McClean PL, McCurtin R, Gault VA, Hölscher C. (2012): Val(8)GLP-1 rescues synaptic plasticity and reduces dense core plaques in APP/PS1 mice. Neurobiol Aging, 33:265-276. First published 2010; DOI:10.1016/j.neurobiolaging.2010.02.014;
Lin Li, Zhi-Feng Zhang, Christian Holscher, Chong Gao, Yuan-Hong Jiang, Yue-Ze Liu (2012): (Val8)glucagon-like peptide-1 prevents tau hyperphosphorylation, impairment of spatial learning and ultra-structural cellular damage induced by streptozotocin in rat brains. Eur J Pharmacol, 674:280-286.
Faivre E., Hamilton A., Holscher C (2012): Effects of acute and chronic administration of GIP analogues on cognition, synaptic plasticity and neurogenesis in mice. Eur J Pharmacol, 674: 294-306.
McClean PL, Parthsarathy V, Faivre E, Hölscher C (2011): The diabetes drug Liraglutide prevents degenerative processes in a mouse model of Alzheimer’s disease. J Neurosci., 31: 6587-6594.
Faivre E., Gault VA, Thorens B, Holscher C (2011): Glucose-dependent insulinotropic polypeptide receptor knockout mice are impaired in learning, synaptic plasticity, and neurogenesis. J Neurophysiol., 105:1574-1580.
Hamilton A., S. Patterson, D. Porter, V. A. Gault and C. Hölscher (2011): Novel GLP-1 mimetics developed to treat type 2 diabetes promote progenitor cell proliferation in the brain. J Neurosci Res, 89:481-489.
Porter DW., Irwin N, Flatt, PR, Holscher C, Gault VA (2010) Prolonged GIP receptor activation improves cognitive function, hippocampal synaptic plasticity and glucose homeostasis in high fat fed mice. Eur J Pharmacol., 650: 688-693.
Wang, Xiao-Hui ; Lin Li, Christian Hölscher, Yan-Fang Pan, Xiao-Rong Chen, Jin-Shun Qi. (2010) Val8-GLP-1 Protects Against Aß1-40-Induced Impairment of Hippocampal Late-Phase Long-Term Potentiation and Spatial Learning in Rats. Neuroscience, 170:1239-1248.
Porter, DW, B.D. Kerr, P.R. Flatt, C. Holscher and V.A. Gault (2010). Four weeks administration of Liraglutide improves memory and learning as well as glycaemic control in mice with high fat dietary-induced obesity and insulin resistance. Diabetes, Obesity and Metabolism, 12:891-899.
Gengler S, Hamilton A, Hölscher C (2010): Synaptic plasticity in the hippocampus of an APP/PS1 mouse model of Alzheimer’s disease is impaired in old but not young mice. PLoS ONE, 5(3):e9764. doi: 10.1371/journal.pone.0009764.
Gault VA, Porter WD, P.R. Flatt, C. Hölscher (2010): Actions of exendin-4 therapy on cognitive function and hippocampal synaptic plasticity in mice fed a high-fat diet. Int J Obesity, 34(8):1341-4.
McClean PL, Gault VA, Harriott P, Holscher C (2010). Glucagon-like peptide-1 analogues enhance synaptic plasticity in the brain: a link between diabetes and Alzheimer’s disease. Eur J Pharmacol, 630:158-162.
Markus Fendt, Hugo Bürki, Stefan Imobersteg, Herman van der Putten, Kevin McAllister, Julian C Leslie, David Shaw, Christian Hölscher. (2010): The effect of mGluR8 deficiency in animal models of psychiatric diseases. Genes, Brain and Behav., 9:33-44.
Li L, Hao J,Wang Z, Holscher C. (2009): Estrogen attenuates over-expression of amyloid precursor protein messenger RNA and inhibits congophilic Aß formation in prefrontal cortex and hippocampus induced by hypercholesterolemiain-ovariectomy rabbits. Chinese Journal of Neuroanatomy. 24: 481-486.
LI L, Li YW, Zhao JY, Hölscher C (2009): Quantitative analysis of iron concentration and ferroportin 1 in the cortex and hippocampus of rats induced by cerebral ischemia. J Clin Neurosci, 16:1466-1472.
Hamilton A, Hölscher C (2009): Receptors for the incretin Glucagon-Like Peptide-1 are expressed on neurons in the CNS. Neuroreport, 20:1161-1166.
Abbas T., Faivre E, Hölscher C. (2009); Impairment of synaptic plasticity and memory formation in GLP-1 receptor KO mice: interaction between type 2 diabetes and Alzheimer’s disease. Behav Brain Res. 205:265-271
Wang R, Wang H, Zhao Z, Zhijuan J; Xu S, Hölscher C, Sheng S (2009) Coexistences of insulin signaling-related proteins and choline acetyltransferase in neurons. Brain Res, 249:237-243.
Hölscher C, van Aalten L, Sutherland C (2008): Anaesthesia generates neuronal insulin resistance by inducing hypothermia. BMC Neuroscience, 9:100-104.
Gault VA, Hölscher C (2008): A novel GIP agonist facilitates hippocampal LTP and reverses the impairment of LTP induced by beta-amyloid. J. Neurophysiol 99:1590-1595.
Gault VA, Hölscher C (2008): GLP-1 agonists facilitate hippocampal LTP and reverse the impairment of LTP induced by beta-amyloid, Eur J Pharmacol, 587:112-117.
Gengler S., Gault VA, Harriott P, Hölscher C. (2007). Beta-amyloid (25-35) induced impairments of hippocampal synaptic plasticity are dependent on stimulation-protocol, genetic background, and aggregation state. Exp Brain Res., 179:621-630.
Holscher C, Gengler S, Gault VA, Patrick Harriott, Hanspeter Mallot HA (2007). Soluble beta-amyloid[25-35] reversibly impairs hippocampal synaptic plasticity and spatial learning. Eur J Pharmacol, 561:85-90.
Radde R, T Bolmont, S A Käser, J Coomaraswamy, D Lindau, L Stoltze, ME Calhoun, F Jäggi, H Wolburg, S Gengler, C Haass, B Ghetti, C Czech, C Hölscher, PM Mathews, M Jucker (2006). Aß42-driven cerebral amyloidosis in transgenic mice reveals early and robust pathology. EMBO Report, 7:940-946.
Hölscher C, Schmid S, Pilz P, van der Putten H, Plappert C (2005): Lack of the metabotropic glutamate receptor subtype 7 selectively modulates theta rhythm and working memory. Learning and Memory, 12:450-455.
Gengler S, Mallot HA, Hölscher C (2005): Inactivation of the rat dorsal striatum impairs performance in spatial tasks and alters hippocampal theta in the freely moving rat. Behav. Brain Res., 164:73-82.
Hölscher C, Schnee A., Dahmen H, Setial L., Mallot HA (2005): Rats are able to navigate in virtual environments. J Exp Biol, 208:561-569.
Hölscher C, Jacob W, Mallot HA (2004): Learned association of allocentric and egocentric information in the hippocampus. Exp Brain Res, 158:233-240
Hölscher C, Schmid S, Pilz P, van der Putten H, Plappert C (2004): Metabotropic glutamate receptor subtype 7 ablation causes a selective deficit in working memory but not long-term memory formation. Behav Brain Res, 154:473-481
Hölscher C, Jacob W, Mallot HA (2003): Reward modulates neuronal activity in the hippocampus of the rat. Behav. Brain Res., 142:181-191.
Hölscher C., Rolls ETR and J-Z Xiang (2003): Perirhinal cortex neuronal activity related to long term memory in the macaque. Eur J Neurosci 18:2037-2046.
Hölscher C., Rolls ETR (2002): Perirhinal cortex neuronal activity related to working memory in the macaque. Neural Plasticity, 9:51-61.
Hölscher C (2002): Different strains of rats show different sensitivity to block of LTP by nitric oxide synthase inhibitors. Eur. J Pharmacol., 457:99-106.
Freir DB, Herron CE and Hölscher C (2001): Blockade of LTP by beta-amyloid fragments in the CA1 region of the rat hippocampus in vivo. J Neurophysiol., 85:708-713.
Freir, DB; Holscher, C; Herron, CE; (2000) ‘beta-amyloid fragments cause depletion of LTP in area CA1 in the in vivo anaesthetised rat’. Journal of Physiology-London, 523:204-205
Hölscher C. (1999): Stress impairs performance in spatial water maze tasks. Behav. Brain Res., 100:225-235.
Hölscher C: (1999): ‘Nitric oxide is required for expression of LTP that is induced by stimulation phase-locked with theta rhythm’- the story continues. Eur. J. Neurosci. 11:2596-2597
Hölscher C. (1999): Nitric oxide is required for expression of LTP that is induced by stimulation phase-locked with theta rhythm. Eur. J. Neurosci., 11:335-344.
Hölscher C. (1998): Beta-amyloid induced reduction in synaptic transmission is reversed by inhibitors of nitric oxide synthase. Neuroreport 9:1245-8.
Xu L., Hölscher C., Anwyl R., Rowan MJ (1998): Glucocorticoid receptor and protein/RNA synthesis-dependent mechanisms underlie the control of synaptic plasticity by stress. Proc Natl Acad Sci USA, 95:3204-3208
McGahon B., Hölscher C., McGlinchey L., Rowan M., Lynch M.A. (1997): Training in the Morris Water maze occludes the synergism between ACPD and arachidonic acid on glutamate release in synaptosomes prepared from rat hippocampus. Learning & Memory 3:296-304.
Hölscher C., McGlinchey L., Anwyl R., Rowan MJ. (1997): HFS-induced long-term potentiation and LFS-induced depotentiation in area CA1 of the hippocampus are not good models for learning. Psychopharmacol., 130:174-182.
Hölscher C., Anwyl R., Rowan MJ. (1997): Block of HFS- induced LTP in the dentate gyrus by 1S,3S-ACPD: Further evidence against LTP as a model for learning. Neuroreport, 8:451-454.
Hölscher C., Anwyl R., Rowan MJ. (1997): Activation of group II metabotropic glutamate receptors blocks induction of long-term potentiation and depotentiation in vivo. Eur. J. Pharmacol., 322:155-163.
Hölscher C., Anwyl R., Rowan MJ. (1997): Block of theta-burst induced LTP by 1S,3S-ACPD: further evidence against LTP as a model for learning. Neurosci., 81:17-22.
Hölscher C., Anwyl R., Rowan MJ. (1997): Stimulation on the positive phase of hippocampal theta rhythm induces long-term potentiation which can be depotentiated by stimulation on the negative phase in area CA1 in vivo. J. Neurosci., 17:6470-6477.
Doyle C., Hölscher C., Rowan M.J., Anwyl R. (1996): The selective neuronal nitric oxide synthase antagonist 7-nitro indazole blocks both long-term potentiation and depotentiation of field excitatory postsynaptic potentials in rat hippocampal CA1 in vivo. J. Neurosci. 16:418-425.
Hölscher C., McGlinchey L., Anwyl R., Rowan M. (1996): 7-Nitro Indazole, a selective neuronal nitric oxide synthase inhibitor, impairs spatial learning in the rat. Learning & Memory 2:267-278.
Hölscher C., McGlinchey L., Rowan M. (1996): L-AP4 (L(+)-2-amino-4-phosphonobutyric acid) induced impairment of spatial learning in the rat is antagonized by MAP4 ((S)-2-amino-2-methyl-4-phosphonobutanoic acid). Behav. Brain Res. 81:69-79.
Hölscher C., McGlinchey L., Anwyl R., Rowan MJ. (1996): Long-term potentiation in area CA1 of the rat hippocampus is not required for spatial learning. J. Neurophys. 495:63P.
Hölscher C., McGlinchey L., Anwyl R., Rowan MJ. (1996): Dissociation of hippocampal LTP and spatial learning by 1S,3S-ACPD. Neuropharmacol. 35:A15.
Hölscher C. (1995): 7-Nitro indazole, a neuron specific nitric oxide synthase inhibitor, produces amnesia in the chick. Learning and Memory 1:213-216
Hölscher C. (1995): Quinacrine acts like an acetylcholine receptor antagonist rather than like a phospholipase A2 inhibitor in a passive avoidance task in the chick. Neurobiology of Learning and Memory 63:206-208.
Hölscher C. (1995): Inhibitors of cyclooxygenases have amnestic effects in a passive avoidance task of the chick. Eur. J. Neurosci. 7:1360-1365.
Hölscher C., Canevari L., Richter-Levin G. (1995): Inhibitors of PLA2 and NO synthase act synergically in producing amnestic effects on spatial learning in the rat. NeuroReport 6:730-734.
Hölscher C., Canevari L., Richter-Levin G. (1995): Two retrograde messengers are better than one? A comment. NeuroReport 6:U6.
Hölscher C. (1995): Release of prostaglandins during memory consolidation in the chick. Eur. J. Pharmacol. 294:253-259.
Hölscher C., Doyle C.A., McGlinchey L., Anwyl R., Rowan M. (1995): A selective neuronal nitric oxide synthase inhibitor impairs spatial learning in the rat. British J. Pharmacol. 115:134.
Hölscher C., Rose S.P.R. (1994): Inhibitors of phospholipase A2 produce amnesia for a passive avoidance task in the chick. Behav. & Neural Biol. 61:225-232
Hölscher C. (1994): Inhibitors of metabotropic glutamate receptors produce amnestic effects in chicks. NeuroReport 5:1037-1040
Hölscher C., W. J. Schmidt (1994): Quinolinic acid lesion of the rat entorhinal cortex pars medialis produces selective amnesia in allocentric working memory (WM), but not in egocentric WM. Behav. Brain Res. 63:187-194.
Hölscher C., Rose S.P.R. (1993): Inhibiting synthesis of the putative retrograde messenger nitric oxide results in amnesia in a passive avoidance task in the chick. Brain Research, 619:189-194
Hölscher C., Rose S.P.R. (1992): An inhibitor of nitric oxide synthesis prevents memory formation in the chick. Neurosci. Lett. 145:165-167
Reviews
Niklas Reich and Christian Hölscher (2022): Beyond appetite: Acylated ghrelin as a learning, memory and fear behavior-modulating hormone. Neuroscience and Biobehavioral Reviews, https://doi.org/10.1016/j.neubiorev.2022.104952.
Niklas Reich and Christian Hölscher (2022): The neuroprotective effects of glucagon-like peptide 1 in Alzheimer’s and Parkinson’s disease: an in-depth review. Frontiers Neuroscience, DOI:10.3389/fnins.2022.970925
C. Hölscher (2022): GLP-1 and GIP peptide hormones and novel receptor agonists protect synapses in Alzheimer and Parkinson’s disease. Frontiers in Synaptic Neuroscience, Open Access.
Xiaoyan Yang, Peng Feng, Rong Ji, Yiqing Ren, Wenshi Wei, Christian Hölscher( 2022): Therapeutic Application of GLP-1 and GIP Receptor agonists in Parkinson’s disease. Expert Opinion on Therapeutic Targets, 26:445-460.
Xiaoyan Yang, Qiang Qiang, Nan Li, Peng Feng, Wenshi Wei, Christian Hölscher (2022): Neuroprotective Mechanisms of Glucagon-like Peptide-1-based Therapies in Ischemic Stroke: An update based on preclinical research. Frontiers Pharmacol., click here.
Rui Chen, Guofang Xue, Christian Hölscher (2021): The role of the TNFα-mediated Astrocyte Signaling Pathway in Epilepsy. Acta Epileptologica, 3:24.
C. Hölscher (2022): Protective properties of GLP-1 and associated peptide hormones in neurodegenerative disorders. British Journal of Pharmacology, 179(4):695-714.
Niklas Reich and Christian Hölscher (2020): Acylated ghrelin as a multi-targeted therapy for Alzheimer’s and Parkinson’s disease. Frontiers Neuroscience, 14:614828. DOI: 10.3389/fnins.2020.614828
Mark P. Maskery, Christian Hölscher, Stephanie Jones, Christopher I. Price, W. David Strain, Caroline Watkins, David Werring, Hedley C.A. Emsley (2020): Glucagon like peptide-1 receptor agonists as neuroprotective agents for ischemic stroke: a systematic scoping review. Journal of cerebral blood flow and metabolism, 41:14-30.
C. Hölscher (2020): Brain insulin resistance: role in neurodegenerative disease and potential for targeting. Expert Opinion on Therapeutic Targets, 29:333-348.
Zhang, ZQ and Hölscher, C. (2020): GIP has neuroprotective effects in Alzheimer and Parkinson’s disease models. Peptides, 125:170184
Christian Hölscher (2019): Insulin signalling impairment in the brain as a risk factor in Alzheimer’s Disease. Frontiers Aging Neuroscience, doi: 10.3389/fnagi.2019.00088.
Christian Hölscher (2019): Moving towards a more realistic concept of what constitutes Alzheimer’s disease. EBioMedicine, DOI:10.1016/j.ebiom.2018.12.030
Christian Hölscher (2018): Novel dual GLP-1/GIP receptor agonists show neuroprotective effects in Alzheimer’s and Parkinson’s disease models. Neuropharmacology, 136:251-259.
Victor A. Gault and Christian Hölscher (2018): GLP-1 receptor agonists show neuroprotective effects in animal models of diabetes. Peptides, 100:101-107.
Yanwei Li, Christian Hölscher (2017): Therapeutic potential of baicalein in Alzheimer’s and Parkinson’s disease. CNS drugs, 31:639-652.
Peng Zhang, Christian Hölscher, Xun Ma (2017): Therapeutic potential of flavonoids in spinal cord injury. Reviews in the Neurosciences, 28:87-101.
C. Hölscher (2016): GLP-1 and GIP analogues as novel treatments for Alzheimer’s and Parkinson’s disease. Cardiovascular Endocrinology, 5(3):93-98.
Yanwei Li, Lin Li, Christian Hölscher (2016): Incretin-based therapy for type 2 diabetes mellitus is promising for treating neurodegenerative diseases. Reviews in the Neurosciences, 27:689-711.
Yanwei Li, Lin Li, Christian Hölscher (2016): Therapeutic potential of genipin in central neurodegenerative diseases. CNS Drugs, 30(10):889-897.
Chenhui Ji, Guo-Fang Xue, Guanglai Li, Dongfang Li, Christian Hölscher (2015): Neuroprotective effects of glucose-dependent insulinotropic polypeptide in Alzheimer’s disease. Reviews in the Neurosciences, 27:61-70.
WeiZhen Liu, GuangLai Li, Christian Hölscher, Lin Li (2015): Neuroprotective effects of geniposide from Alzheimer’s disease pathology. Reviews in the Neurosciences, 26:271-383.
Hölscher C. (2014): New drug treatments show effects in Alzheimer’s and Parkinson’s disease. Neural Regeneration Research, 9(21):1870-1873.
Sharma M. and Hölscher C. (2014): The Neurophysiological and Neuroprotective effects of Leptin. JSM Alzheimer’s Dis Related Dementia, 1(2):1009pp.
Hölscher, C. (2014): Peptide drugs that have been developed to treat type 2 diabetes show neuroprotective effects. Reg Pep, 192-193:55-56. DOI:10.1016/j.regpep.2014.05.002
Hölscher C. (2014): Drugs developed for treatment of diabetes show protective effects in Alzheimer’s and Parkinson’s disease. Acta Physiologica Sinica, 66(5):497-519.
Hölscher C. (2014): Insulin, incretins and other growth factors as potential novel treatments for Alzheimer’s and Parkinson’s disease. Biochemical Society Transactions, 42:593-599.
Hölscher C. (2014): Editorial.
Alzheimers Dement, 10(1 Suppl):S1-2. doi: 10.1016/j.jalz.2013.12.016.
Hölscher C. (2014): First clinical data of the neuroprotective effects of nasal insulin application in patients with Alzheimer’s disease. Alzheimers Dement, 10(1S):S33-S37. doi: 10.1016/j.jalz.2013.12.006.
Hölscher C. (2014): The incretin hormones glucagonlike peptide 1 and glucose-dependent insulinotropic polypeptide are neuroprotective in mouse models of Alzheimer’s disease. Alzheimers Dement, 10(1S):S47-S54. doi: 10.1016/j.jalz.2013.12.009.
Hölscher C (2014): Central effects of GLP-1: new opportunities for treatments of neurodegenerative diseases. J Endocrinol., 221:31-41.
Gao C, Liu Y, Li L, Hölscher C. (2013): New animal models of Alzheimer’s disease that display insulin desensitization in the brain. Rev Neurosci. 2013;24:607-615.
Jessica Freiherr, Manfred Hallschmid, William H. Frey II, Yvonne F. Brünner, Colin D. Chapman, Christian Hölscher, Suzanne Craft, Fernanda G. De Felice, Christian Benedict (2013): Intranasal Insulin as a Treatment for Alzheimer’s Disease: A Review of Basic Research and Clinical Evidence. CNS drugs, 27:505-514.
Hölscher C (2012): Potential Roles of Glucagon-Like Peptide-1 (GLP-1) in Neuroprotection. CNS drugs, 26:871-882.
Chong Gao, Christian Hölscher, Yueze Liu, Lin Li (2012): GSK3: A key target for the development of novel treatments for Type 2 Diabetes Mellitus and Alzheimer disease. Rev Neurosci., 23:1-11.
Hölscher C (2011): Diabetes as a risk factor for Alzheimer’s disease: insulin signalling impairment in the brain as an alternative model of Alzheimer’s disease. Biochem Soc Trans, 31:891-897.
Hölscher C, Li L (2010): New roles for insulin-like hormones in neuronal signalling and protection: new hopes for novel treatments of Alzheimer’s Disease? Neurobiol Aging, 31:1495-1502.
Hölscher, C (2010): Incretin analogues that have been developed to treat type 2 diabetes hold promise as a novel treatment strategy for Alzheimer’s disease. Recent Patents on CNS Drug Discovery, 5: 109-117.
Li L, Hölscher C (2007): Common pathological processes in Alzheimer Disease and Type 2 Diabetes: a review. Brain Res Rev, 23:58-65.
Hölscher C. (2005): Development of beta-amyloid-induced neurodegeneration in Alzheimer’s disease and novel neuroprotective strategies. Reviews in the Neurosciences, 16:181-212.
Hölscher C. (2003): Time, space, and hippocampal functions. Reviews in the Neurosciences, 14:253-284.
Hölscher C. (2002): Metabotropic glutamate receptors control gating of spike transmission in the hippocampus. Pharmacol Biochem Behavior, 73(2):307-316.
Hölscher C., J. Gigg, O’Mara S. (1999): Metabotropic Glutamate Receptor Activation and Blockade. Consequences for long-term potentiation, learning and neurotoxicity. Neurosci. Biobeh. Rev., 23:399-410.
Hölscher C. (1999): Synaptic plasticity and learning and memory: LTP and beyond. J Neurosci Res 58:62-75.
Hölscher C. (1999): Consciousness in mind: a correlate for ACh? A comment. Trends Neurosci. 22:541-543.
Hölscher C. (1998): Possible causes of Alzheimer’s disease: amyloid fragments, free radicals, and calcium homeostasis. Neurobiology of disease, 5:129-141.
Hölscher C. (1997): Long-term potentiation: a good model for learning and memory? Progr. Neuro-Psychopharmacol. & Biol. Psychiat., 21:47-68.
Hölscher C. (1997): NO, the enigmatic neuronal messenger: Its role in synaptic plasticity. Trends Neurosci., 20:298-303.
Books
‘Mechanisms of information processing in the Brain: Information Processing by Neuronal Populations’. C Holscher and M Munk (Eds.). Cambridge University Press, Cambridge UK. 2008, ISBN 978-0-521-87303-1
Neuronal mechanisms of memory formation: Concepts of long term potentiation and beyond. C. Hölscher (Ed.). Cambridge University Press, 2001. ISBN 0-521-77067-X.
Paperback reprint of this book ISBN 0-521-01803-X, Cambridge University Press, 2005
Book Chapters
Hölscher C, (2020): Chapter 3: Evidence for Pathophysiological Commonalities between Metabolic and Neurodegenerative Disorders. In: Metabolic Drivers and Bioenergetic Components of Neurodegenerative Disease Volume 155, Elsevier. ISBN: 978-0-12-820076-6
Hölscher C, (2017): Neuroscience and Biobehavioural Psychology. Section 1. Growth Factors: Neuronal Atrophy. Elsevier. P1-8. ISBN 9780128093245
Hölscher C, (2012): Novel incretin analogues developed to treat type 2 diabetes as a potential treatment for Alzheimer’s disease. In: L.M. Botana (Ed.), ‘Therapeutical targets: Modulation, Inhibition, and Activation’, chapter 10. Wiley-Blackwell. ISBN: 978-0-470-58719-5
Hölscher C, (2011): Protective roles of the incretin hormones Glucagon-Like Peptide-1 and Glucose-dependent Insulinotropic Polypeptide hormones in neurodegeneration. In: (S De la Monte, Ed.) “Alzheimer’s Disease Pathogenesis-Core Concepts, Shifting Paradigms and Therapeutic Targets”, Chapter 29, InTech publishing, ISBN: 978-953-307-690-4.
Hölscher C (2010): Höhere Verarbeitungsprozesse im Gehirn. In: Taschenlehrbuch Biologie, Zoologie, K. Munk (editor), Thieme, ISBN 978-3-13-144841-5.
Hölscher C, (2010): The role of GLP-1 in neuronal activity and neurodegeneration. In: Vitamins and Hormones, volume 84, INCRETINS AND INSULIN SECRETION, Academic Press/Elsevier, Chapter 13, pp 331-354. ISBN: 978-0-12-381517-0.
Hölscher (2008): Functional roles of Theta and Gamma oscillations in the association and dissociation of neuronal networks in primates and rodents. Chapter 7, in: Information Processing by Neuronal Populations, Hölscher and Munk (Eds)., Cambridge University Press, ISBN 978-0-521-87303-1
Hölscher C (2008) How could populations of neurons encode information?. Chapter 1, in: Information Processing by Neuronal Populations, Hölscher and Munk (Eds)., Cambridge University Press, ISBN 978-0-521-87303-1
Hölscher, C (2004): Phospholipases – their role in memory formation. In: Cellular mechanisms of memory formation. (Riedel, Platt, Eds.), Landes Biosciences, USA.
Hölscher, C (2002): Höhere Verarbeitungsprozesse im ZNS. Lehrbuch Grundstudium Biologie, Zoologie Band, Kapitel 6. Spektrum Verlag, Heidelberg.
Hölscher C. (2001): Long-term potentiation as a model for memory mechanisms: The story so far. In: Neuronal mechanisms of memory formation (Hölscher, ed.), Cambridge University Press, pp. 1-37.
Hölscher C. (2001): Long-term potentiation induced by stimulation on the positive phase of theta rhythm: a better model for learning and memory? In: Neuronal mechanisms of memory formation (Hölscher, ed.), Cambridge University Press, pp. 146-167.
Hölscher C, Bliss, TVP, Richter–Levin, G (2001): Conclusions and future targets in memory research. In: Neuronal mechanisms of memory formation (Hölscher, ed.), Cambridge University Press, pp. 476-491.
Hölscher C., O’Mara S. (1997): “Model Learning and Memory systems in Neurobiological Research: Conditioning and Associative Learning Procedures and Spatial Learning Paradigms”, Chapter XI, pp81-93. Eds. Lynch and O’Mara, Neuroscience Labfax manual, Academic Press.
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