Therapeutic application of GLP-1 and GIP receptor agonists in Parkinson's disease

被引：34
作者：
Yang, Xiaoyan [1 ]
Feng, Peng [2 ]
Ji, Rong [1 ]
Ren, Yiqing [1 ]
Wei, Wenshi [1 ]
Holscher, Christian [2 ,3 ]
机构：
[1] Fudan Univ, Dept Neurol, Huadong Hosp, 221 West Yanan Rd, Shanghai, Peoples R China
[2] Shanxi Med Univ, Dept Neurol, Affiliated Hosp 2, Taiyuan, Peoples R China
[3] Henan Univ Tradit Chinese Med, Acad Chinese Med Sci, Zhengzhou, Peoples R China
来源：
EXPERT OPINION ON THERAPEUTIC TARGETS | 2022年 / 26卷 / 05期
关键词：
Parkinson's disease; diabetes; insulin resistance; Glucagon-like peptide 1; GIP; inflammation; autophagy; GLUCAGON-LIKE PEPTIDE-1; MPTP MOUSE MODEL; DEPENDENT INSULINOTROPIC POLYPEPTIDE; DIPEPTIDYL PEPTIDASE-4 INHIBITORS; ALZHEIMERS-DISEASE; GLUCOSE-METABOLISM; DIABETES-MELLITUS; OXIDATIVE STRESS; MITOCHONDRIAL DYSFUNCTION; AUTOPHAGIC DEGRADATION;
D O I：
10.1080/14728222.2022.2079492
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
Introduction Diabetes is a risk factor for Parkinson's disease (PD) and shares similar dysregulated insulin pathways. Glucagon-like peptide-1 (GLP-1) analogs originally designed to treat diabetes have shown potent neuroprotective activity in preclinical studies of PD. They are neuroprotective by inhibiting inflammation, improving neuronal survival, maintenance of synapses, and dopaminergic transmission in the brain. Building on this, three clinical studies have reported impressive effects in patients with PD, testing -4 (Exenatide, Bydureon) or liraglutide (Victoza, Saxenda). Glucose-dependent insulinotropic peptide (GIP) is another peptide hormone that has shown good effects in animal models of PD. Novel dual GLP-1/GIP agonists have been developed that can penetrate the blood-brain barrier (BBB) and show superior effects in animal models compared to GLP-1 drugs. Areas covered The review summarizes preclinical and clinical studies testing GLP-1R agonists and dual GLP-1/GIPR agonists in PD and discusses possible mechanisms of action. Expert opinion Current strategies to treat PD by lowering the levels of alpha-synuclein have not shown effects in clinical trials. It is time to move on from the 'misfolding protein' hypothesis. Growth factors such as GLP-1 that can cross the BBB have already shown impressive effects in patients and are the future of drug discovery in PD.
引用
收藏
页码：445 / 460
页数：16
相关论文
共 239 条
[1]  
AbbVie, CIT STRAT CONS ABBVI
[2]   Lixisenatide, a novel GLP-1 analog, protects against cerebral ischemia/reperfusion injury in diabetic rats [J].
Abdel-latif, Rania G. ;
Heeba, Gehan H. ;
Taye, Ashraf ;
Khalifa, Mohamed M. A. .
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, 2018, 391 (07) :705-717
[3]   Antidiabetic Drugs for the Risk of Alzheimer Disease in Patients With Type 2 DM Using FAERS [J].
Akimoto, Hayato ;
Negishi, Akio ;
Oshima, Shinji ;
Wakiyama, Haruna ;
Okita, Mitsuyoshi ;
Horii, Norimitsu ;
Inoue, Naoko ;
Ohshima, Shigeru ;
Kobayashi, Daisuke .
AMERICAN JOURNAL OF ALZHEIMERS DISEASE AND OTHER DEMENTIAS, 2020, 35
[4]  
Aksoy D, 2017, AM J MED SCI, V354, P319, DOI 10.1016/j.amjms.2017.05.002
[5]   Pathogenesis-Targeted, Disease-Modifying Therapies in Parkinson Disease [J].
AlDakheel, Amaal ;
Kalia, Lorraine V. ;
Lang, Anthony E. .
NEUROTHERAPEUTICS, 2014, 11 (01) :6-23
[6]   GDNF, NGF and BDNF as therapeutic options for neurodegeneration [J].
Allen, Shelley J. ;
Watson, Judy J. ;
Shoemark, Deborah K. ;
Barua, Neil U. ;
Patel, Nikunj K. .
PHARMACOLOGY & THERAPEUTICS, 2013, 138 (02) :155-175
[7]   The expression of GLP-1 receptor mRNA and protein allows the effect of GLP-1 on glucose metabolism in the human hypothalamus and brainstem [J].
Alvarez, E ;
Martínez, MD ;
Roncero, I ;
Chowen, JA ;
García-Cuartero, B ;
Gispert, JD ;
Sanz, C ;
Vázquez, P ;
Maldonado, A ;
de Cáceres, J ;
Desco, M ;
Pozo, MA ;
Blázquez, E .
JOURNAL OF NEUROCHEMISTRY, 2005, 92 (04) :798-806
[8]  
Alzheimer A., 1907, Allg. Z. Psychiatr, V64, P146
[9]   Insulin resistance and Parkinson's disease: A new target for disease modification? [J].
Athauda, D. ;
Foltynie, T. .
PROGRESS IN NEUROBIOLOGY, 2016, 145 :98-120
[10]   Utility of Neuronal-Derived Exosomes to Examine Molecular Mechanisms That Affect Motor Function in Patients With Parkinson Disease A Secondary Analysis of the Exenatide-PD Trial [J].
Athauda, Dilan ;
Gulyani, Seema ;
Karnati, Hanuma Kumar ;
Li, Yazhou ;
Tweedie, David ;
Mustapic, Maja ;
Chawla, Sahil ;
Chowdhury, Kashfia ;
Skene, Simon S. ;
Greig, Nigel H. ;
Kapogiannis, Dimitrios ;
Foltynie, Thomas .
JAMA NEUROLOGY, 2019, 76 (04) :420-429
12345678910