α-synuclein aggregation and its modulation

Parkinson's disease (PD) is a neurological disorder marked by the presence of cytoplasmic inclusions, Lewy bodies (LBs) and Lewy neurites (LNs) as well as the degeneration of dopamine producing neurons in the substantia nigra region of the brain. The LBs and LNs in PD are mainly composed of aggregated form of a presynaptic protein, alpha-synuclein (alpha-Syn). However, the mechanisms of alpha-Syn aggregation and actual aggregated species responsible for the degeneration of dopaminergic neurons have not yet been resolved. Despite the fact that alpha-Syn aggregation in LBs and LNs is crucial and mutations of alpha-Syn are associated with early onset PD, it is really a challenging task to establish a correlation between alpha-Syn aggregation rate and PD pathogenesis. Regardless of strong genetic contribution, PD is mostly sporadic and familial forms of the disease represent only a minor part (<10%) of all cases. The complexity in PD further increases due to the involvement of several cellular factors in the pathogenesis of the disease as well as the environmental factors associated with the risk of developing PD. Therefore, effect of these factors on alpha-Syn aggregation pathway and how these factors modulate the properties of wild type (WT) as well as mutated alpha-Syn should be collectively taken into account. The present review specifically provides an overview of recent research on alpha-Syn aggregation pathways and its modulation by several cellular factors potentially relevant to PD pathogenesis. We also briefly discuss about effect of environmental risk factors on alpha-Syn aggregation. (C) 2016 Elsevier B.V. All rights reserved.