Alpha-Synuclein Pathophysiology in Neurodegenerative Disorders: A Review Focusing on Molecular Mechanisms and Treatment Advances in Parkinson’S Disease Publisher Pubmed



Yaribash S¹ ; Mohammadi K^{2, 3} ; Sani MA⁴ Show Affiliations
Source: Cellular and Molecular Neurobiology Published:2025

Abstract

Worldwide aging has contributed to the growth of prevalence of neurodegenerative diseases (NDDs), including Parkinson’s disease among the elderlies. The advanced destruction of dopaminergic neurons in the substantia nigra, due to many accelerator factors in the brain is the main mechanism of Parkinson’s disease. The pathological aggregated alpha-synuclein (α-syn), a protein implicated in multiple neurodegenerative disorders, is one of the critical factors in this neurodegenerative disease and other similar disorders. The misfolding and aggregation of α-syn may interrupt critical processes, including functions of synaptic vesicles and can lead to neuronal death. This protein is encoded by Alpha-Synuclein Gene (SNCA) and mutation in this gene can lead to dysfunctions of the protein structure. Since, therapeutic policies that aim α-syn are promising approaches. Advances in immunotherapies, molecular chaperones, gene therapy targeting SNCA, and DNA aptamers are some examples of this strategy. This review aims to comprehensively assess the current knowledge and evidence on α-syn pathology, genetic determinants, and novel therapeutic methods in Parkinson,’s disease and other synucleinopathies. Continued investigation to discover interventions in this system could result in finding of effective and safe treatments for NDDs. © The Author(s) 2025.