Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
6271844 | Neuroscience | 2015 | 9 Pages |
â¢Liraglutide and lixisenatide protect mice from MPTP toxicity, a model of Parkinson's disease.â¢Both drugs are currently on the market to treat type 2 diabetes.â¢Neuroprotective effects in PD are shown for the first time here.â¢Clinical trials are in preparation in Parkinson's patients, testing these drugs.
Glucagon-like peptide 1 (GLP-1) is a growth factor. GLP-1 mimetics are on the market as treatments for type 2 diabetes and are well tolerated. These drugs 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 clinical trial in PD patients showed promising first results. Liraglutide and lixisenatide are two newer GLP-1 mimetics which have a longer biological half-life than exendin-4. We previously showed that these drugs have neuroprotective properties in an animal model of Alzheimer's disease. Here we demonstrate the neuroprotective effects in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. MPTP was injected once-daily (20Â mg/kg i.p.) for 7Â days, and drugs were injected once-daily for 14Â days i.p. When comparing exendin-4 (10Â nmol/kg), liraglutide (25Â nmol/kg) and lixisenatide (10Â nmol/kg), it was found that exendin-4 showed no protective effects at the dose chosen. Both liraglutide and lixisenatide showed effects in preventing the MPTP-induced motor impairment (Rotarod, open-field locomotion, catalepsy test), reduction in tyrosine hydroxylase (TH) levels (dopamine synthesis) in the substantia nigra and basal ganglia, a reduction of the pro-apoptotic signaling molecule BAX and an increase in the anti-apoptotic signaling molecule B-cell lymphoma-2. The results demonstrate that in this study, both liraglutide and lixisenatide are superior to exendin-4, and both drugs show promise as a novel treatment of PD.