Novel Therapeutic Strategies in Targeting Alpha Synuclein Dysfunction Pathways for Parkinson’s Disease Treatment

Abstract: Parkinson’s disease (PD) is a neurodegenerative, progressive disorder presenting with both motor and non-motor symptoms. Its pathogenesis likely results from dysfunction of the presynaptic protein alpha-synuclein, which produces neuronal toxicity and aggregation in Lewy bodies. Relevant literature was identified through systematic searches in PubMed, Scopus, Web of Science, and Google Scholar using a range of descriptors in English. In this review, we investigated novel therapeutic strategies targeting alpha-synuclein, including small molecule inhibitors, immunotherapies, RNA-based therapies, and protein clearance mechanisms. It also reviews our recent advances in nanotechnological development for drug delivery systems to enhance therapeutic efficacy using lipid- based nanoparticles, polymeric carriers, and exosome delivery. Although much progress has been achieved, including clinical translation, biomarker development, and large-scale production, many challenges still remain. With the help of emerging trends such as AI-driven nanotechnology and personalized medicine, these gaps can be targeted. We emphasize the importance of integrated and multi-targeted approaches for the development of effective disease-modifying therapies for PD.