title: Neuroprotective effects of (Val8)GLP-1-Glu-PAL in the MPTP Parkinson's disease mouse model.
abstract: Glucagon-like peptide 1 (GLP-1) is a hormone and a growth factor. GLP-1 mimetics are currently on the market as treatments for type 2 diabetes. They also have shown neuroprotective properties in animal models of neurodegenerative disorders. In addition, the GLP-1 mimetic exendin-4 has shown protective effects in animal models of Parkinson's disease (PD), and a first clinical trial in PD patients showed promising results. (Val8)GLP-1-glu-PAL is a new GLP-1 analogue which has a longer biological half-life than exendin-4. We previously showed that (Val8)GLP-1-glu-PAL has neuroprotective properties. Here we tested the drug in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. MPTP was injected (30mg/kg i.p.) along with (Val8)GLP-1-glu-PAL (25nmol/kg i.p.) once-daily for 8 days. (Val8)GLP-1-glu-PAL showed good effects in preventing the MPTP-induced motor impairment (Rotarod, open field locomotion, swim test), reduction in tyrosine hydroxylase levels (dopamine synthesis) in the substantia nigra, a reduction of activated caspase 3 levels, of TUNEL positive cell numbers, of the pro-apoptotic signaling molecule BAX and an increase in the growth signaling molecule Bcl-2. The results demonstrate that (Val8)GLP-1-glu-PAL shows promise as a novel treatment of PD.
authors.affiliation: Key Laboratory of Cellular Physiology, Shanxi Medical University, Taiyuan, Shanxi, PR China.
authors.forename: YanFang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Cellular Physiology, Shanxi Medical University, Taiyuan, Shanxi, PR China.
authors.forename: YiMei
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Key Laboratory of Cellular Physiology, Shanxi Medical University, Taiyuan, Shanxi, PR China. Electronic address: linlilin999@163.com.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.affiliation: Biomedical and Life Science, Faculty of Health and Medicine, Lancaster University, Lancaster LA1 4YQ, UK; Second hospital, Shanxi Medical University, Taiyuan, Shanxi, PR China.
authors.forename: Christian
authors.initials: C
authors.lastname: Hölscher
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000704:Analysis of Variance; D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000187:drug effects; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives* / Q000627:therapeutic use; D055666:Lipopeptides / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D020734:Parkinsonian Disorders / Q000139:chemically induced* / Q000517:prevention & control*; D045442:Rotarod Performance Test; D013550:Swimming / Q000523:psychology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: C583431:(Val8)GLP-1-Glu-PAL; D055666:Lipopeptides; D018696:Neuroprotective Agents; D052216:Glucagon-Like Peptide 1; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase; D053148:Caspase 3
keywords: Apoptosis; Growth factors; Incretin; Insulin; Neuroinflammation; Neuroprotection