Unraveling the role of CGRP in neurological diseases: a comprehensive exploration to pathological mechanisms and therapeutic implications.

Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), Multiple sclerosis (MS), Amyotrophic lateral sclerosis (ALS), and Spinal muscular atrophy (SMA) are neurodegenerative diseases (NDDs) characterized by progressive neuronal degeneration. Recent studies provide compelling information regarding the contribution of Calcitonin Gene-Related Peptide (CGRP), a potent neuropeptide, in regulating neuroinflammation, vasodilation, and neuronal survival in these disorders. This review systematically delves into the multidimensional aspects of CGRP as both a neuroprotective agent and a neurotoxic factor in NDDs. The neuroprotective effects of CGRP include suppression of inflammation, regulation of intracellular signaling pathways, and promotion of neuronal growth and survival. However, under pathological conditions, its overexpression or dysregulation is associated with oxidative stress, excitotoxicity, and neuronal death. The therapeutic use of CGRP and its receptor antagonists in migraine provides substantial evidence for CGRP's therapeutic potential, which can be further explored for the management of NDDs. However, since the bidirectional nature of CGRP effects is evident, it is crucial to gain an accurate insight into its mechanisms to target only the neuropeptide's beneficial effects while completely avoiding the undesired consequences. Further studies should focus on understanding the context-dependent activity of CGRP in the hope of designing targeted therapy for NDDs, which could gradually transform the current pharmacological management of NDDs.