α-synuclein toxicity in neurodegeneration: mechanism and therapeutic strategies

Alterations in a-synuclein dosage lead to familial Parkinson's disease (PD), and its accumulation results in synucleinopathies that include PD, dementia with Lewy bodies (DLB) and multiple system atrophy (MSA). Furthermore, alpha-synuclein contributes to the fibrilization of amyloid-beta and tau, two key proteins in Alzheimer's disease, which suggests a central role for alpha-synuclein toxicity in neurodegeneration. Recent studies of factors contributing to alpha-synuclein toxicity and its disruption of downstream cellular pathways, have expanded our understanding of disease pathogenesis in synucleinopathies.