Neuroprotective role of (Val(8))GLP-1-Glu-PAL in an in vitro model of Parkinson's disease.

The growth factor glucagon-like peptide-1 (GLP-1) is neuroprotective in several animal models of neurodegeneration. Here, we analyzed the neuroprotective effects of a novel protease-resistant GLP-1 analogue, (Val(8))GLP-1-Glu-PAL, which has advantages over older analogues, such as improvement of hippocampal neurogenesis, glucose homeostasis, and insulin secretion. We established an in vitro model of Parkinson's disease using the mitochondrial stressor rotenone in primary cultured mouse neurons pretreated with (Val(8))GLP-1-Glu-PAL. (Val(8))GLP-1-Glu-PAL alone did not affect neuronal viability, but prevented the rotenone-induced reduction in cell viability in a dose-dependent manner. In addition, (Val(8))GLP-1-Glu-PAL pretreatment prevented rotenone-induced proapoptotic changes manifesting as downregulation of procaspase-3 and Bcl-2 and upregulation of cleaved caspase-3. These results demonstrate that the novel agent (Val(8))GLP-1-Glu-PAL shows promise as a drug treatment for Parkinson's disease.