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The neuroprotective effects of glucagon-like peptide 1 in Alzheimer's and Parkinson's disease: An in-depth review.

作者信息

Reich Niklas, Hölscher Christian

机构信息

Biomedical and Life Sciences Division, Faculty of Health and Medicine, Lancaster University, Lancaster, United Kingdom.

Neurology Department, Second Associated Hospital, Shanxi Medical University, Taiyuan, China.

出版信息

Front Neurosci. 2022 Sep 1;16:970925. doi: 10.3389/fnins.2022.970925. eCollection 2022.


DOI:10.3389/fnins.2022.970925
PMID:36117625
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9475012/
Abstract

Currently, there is no disease-modifying treatment available for Alzheimer's and Parkinson's disease (AD and PD) and that includes the highly controversial approval of the Aβ-targeting antibody aducanumab for the treatment of AD. Hence, there is still an unmet need for a neuroprotective drug treatment in both AD and PD. Type 2 diabetes is a risk factor for both AD and PD. Glucagon-like peptide 1 (GLP-1) is a peptide hormone and growth factor that has shown neuroprotective effects in preclinical studies, and the success of GLP-1 mimetics in phase II clinical trials in AD and PD has raised new hope. GLP-1 mimetics are currently on the market as treatments for type 2 diabetes. GLP-1 analogs are safe, well tolerated, resistant to desensitization and well characterized in the clinic. Herein, we review the existing evidence and illustrate the neuroprotective pathways that are induced following GLP-1R activation in neurons, microglia and astrocytes. The latter include synaptic protection, improvements in cognition, learning and motor function, amyloid pathology-ameliorating properties (Aβ, Tau, and α-synuclein), the suppression of Ca deregulation and ER stress, potent anti-inflammatory effects, the blockage of oxidative stress, mitochondrial dysfunction and apoptosis pathways, enhancements in the neuronal insulin sensitivity and energy metabolism, functional improvements in autophagy and mitophagy, elevated BDNF and glial cell line-derived neurotrophic factor (GDNF) synthesis as well as neurogenesis. The many beneficial features of GLP-1R and GLP-1/GIPR dual agonists encourage the development of novel drug treatments for AD and PD.

摘要

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本文引用的文献

[1]
Glucagon-like peptide 1 and glucose-dependent insulinotropic peptide hormones and novel receptor agonists protect synapses in Alzheimer's and Parkinson's diseases.

Front Synaptic Neurosci. 2022-7-27

[2]
Therapeutic application of GLP-1 and GIP receptor agonists in Parkinson's disease.

Expert Opin Ther Targets. 2022-5

[3]
(D-Ser2) oxyntomodulin recovers hippocampal synaptic structure and theta rhythm in Alzheimer's disease transgenic mice.

Neural Regen Res. 2022-9

[4]
L-dopa-Dependent Effects of GLP-1R Agonists on the Survival of Dopaminergic Cells Transplanted into a Rat Model of Parkinson Disease.

Int J Mol Sci. 2021-11-16

[5]
Liraglutide ameliorates diabetes-associated cognitive dysfunction via rescuing autophagic flux.

J Pharmacol Sci. 2021-11

[6]
GLP-1 Receptor Agonists: Beyond Their Pancreatic Effects.

Front Endocrinol (Lausanne). 2021

[7]
Liraglutide Alleviates Cognitive Deficit in db/db Mice: Involvement in Oxidative Stress, Iron Overload, and Ferroptosis.

Neurochem Res. 2022-2

[8]
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 Alzheimers Dis. 2021

[9]
HBXIP accelerates glycolysis and promotes cancer angiogenesis via AKT/mTOR pathway in bladder cancer.

Exp Mol Pathol. 2021-8

[10]
How glucagon-like peptide 1 receptor agonists work.

Endocr Connect. 2021-7-17

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