Intersecting molecular pathways in Synucleinopathies and Amyloidogenesis: Exploring shared mechanisms and therapeutic potential

Abstract

Synucleinopathies and amyloidogenic disorders are the two most prevalent neurodegenerative conditions, characterized by progressive loss of neurons and aggregation of proteins in the central nervous system. Emerging evidence suggests that despite their distinct pathological hallmarks: α-synuclein in Parkinson’s disease (PD) and amyloid-β in Alzheimer’s disease (AD), both disorders share common molecular pathways, including oxidative stress, neuroinflammation, misfolding/aggregation of proteins and mitochondrial dysfunction. This review explores the molecular intersections between synucleinopathies and amyloidogenesis. Furthermore, this review highlights how these pathways drive neuronal loss and suggest that targeting them could provide broad therapeutic benefits. By elucidating the shared mechanisms between PD and AD, the multi-targeted therapies could address the underlying molecular disruptions common to both disorders, offering new avenues for effective disease-modifying treatments in neurodegenerative diseases.