Parkinson’s Disease

Abstract Parkinson’s disease is a disease of aging, but there are several evolved characteristics that make humans susceptible. Alpha-synuclein, the key molecule involved in Parkinson’s disease pathogenesis, is a double-edged sword. Misfolded alpha-synuclein aggregated in Lewy bodies can propagate in prion-like fashion, resulting in Parkinson’s disease. However, alpha-synuclein protects neurons from certain viral infections. This protective role may explain the broad phylogenetic distribution of the synuclein molecules in the animal kingdom. Evolved anatomic features of dopaminergic neurons in the human brain may make them particularly susceptible to neurodegeneration and Parkinson’s disease. Some evidence suggests that relaxation of selection against genes associated with late-life Parkinson’s disease may play a role in this age-related disorder. Finally, mismatch involving environmental exposures, especially pesticides and herbicides, appears important in Parkinson’s disease pathogenesis.