Alpha-synuclein aggregation in Parkinson's disease.

Abstract

Alpha-synuclein (α-Syn) aggregation is closely linked to the pathogenesis of Parkinson's disease, where misfolded monomers form toxic oligomers and amyloid fibrils, which accumulate as Lewy bodies. Several factors, such as genetic mutations, interactions with lipids and proteins such as p62 and ubiquitin, as well as, environmental conditions, e. g. the presence of toxic metals that lead to oxidative stress. Advances in understanding the molecular mechanisms of Parkinson's disease have driven the search for novel therapies, including strategies to inhibit α-Syn aggregation and reduce its cytotoxicity consequently. Natural compounds, such as Skullcapflavone II, and synthetic ones, such 4-triazole phenylamides and phenethylamides, have demonstrated to reduce α-Syn fibrillation and aggregation. This chapter discusses the most recent therapeutic strategies in the treatment of Parkinson's disease concerning the implications of α-Syn.