Neuroprotective effects of (Val8)GLP-1-Glu-PAL in the MPTP Parkinson's disease mouse model

Zhang, YanFang and Chen, YiMei and Li, Lin and Holscher, Christian (2015) Neuroprotective effects of (Val8)GLP-1-Glu-PAL in the MPTP Parkinson's disease mouse model. Behavioural Brain Research, 293. pp. 107-113. ISSN 0166-4328

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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.

Item Type:
Journal Article
Journal or Publication Title:
Behavioural Brain Research
Additional Information:
This is the author’s version of a work that was accepted for publication in Behavioural Brain Research. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Behavioural Brain Research, 293, 2015 DOI: 10.1016/j.bbr.2015.07.021
Uncontrolled Keywords:
/dk/atira/pure/subjectarea/asjc/2800/2802
Subjects:
ID Code:
75651
Deposited By:
Deposited On:
17 Dec 2015 09:46
Refereed?:
Yes
Published?:
Published
Last Modified:
24 Nov 2020 03:33