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val8-glp-1-glu-pal is a long-acting, protease-resistant analogue of glucagon-like peptide-1 (GLP-1), designed with a valine substitution at position 8 and conjugated to a glutamic acid-fatty acid (Glu-PAL) moiety to increase stability and prolong its biological half-life. It acts as an agonist at the GLP-1 receptor, promoting neuroprotective effects, as demonstrated in in vitro and in vivo preclinical models of Parkinson's disease, where it reduced markers of neuronal apoptosis and improved survival of dopaminergic neurons. The drug also improves hippocampal neurogenesis, glucose homeostasis, and insulin secretion in animal models. Its mechanism of action involves activation of GLP-1 receptor signaling, leading to inhibition of pro-apoptotic signals (e.g., caspase-3, BAX) and upregulation of anti-apoptotic proteins (e.g., Bcl-2), thereby preventing neurodegeneration. val8-glp-1-glu-pal shows promise for development as a disease-modifying therapy for neurodegenerative diseases, particularly Parkinson's disease[1][2].
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