Research reportRole of neurotoxicants and traumatic brain injury in α-synuclein protein misfolding and aggregation

•Principle features of various Synuclein protein family members are highlighted.•New findings on metal-induced α-Syn misfolding & consequences are emphasized.•Important effects of pesticides on α-Syn and neurodegeneration are illustrated.•Role of TBI and oxidative stress on α-Syn and neurodegeneration is highlighted.

Protein misfolding and aggregation are key pathological features of many neurodegenerative diseases including Parkinson's disease (PD) and other forms of human Parkinsonism. PD is a complex and multifaceted disorder whose etiology is not fully understood. However, several lines of evidence support the multiple hit hypothesis that genetic vulnerability and environmental toxicants converge to trigger PD pathology. Alpha-synuclein (α-Syn) aggregation in the brain is an important pathophysiological characteristic of synucleinopathies including PD. Epidemiological and experimental studies have shown that metals and pesticides play a crucial role in α-Syn aggregation leading to the onset of various neurodegenerative diseases including PD. In this review, we will emphasize key findings of several epidemiological as well as experimental studies of metal- and pesticide-induced α-Syn aggregation and neurodegeneration. We will also discuss other factors such as traumatic brain injury and oxidative insult in the context of α-Syn-related neurodegenerative processes.

Graphical abstractDownload high-res image (118KB)Download full-size image