Parkinson’s Disease: Etiology, Neuropathology, and Pathogenesis

Parkinson’s disease (PD) is a common neurodegenerative disorder. While a number of nonmotor manifestations arise, the typical clinical features involve a movement disorder consisting of bradykinesia, resting tremor, and rigid­ity, with postural instability occurring at a later stage. The cause of PD is not known, but a number of genetic risk factors have now been characterized, as well as several genes which cause rare familial forms of PD. Environmental influences such as smoking, caffeine consumption, and pesticide exposure have been postulated to alter the risk of PD development, although the role of these remains unclear. The movement disorder arises due to the loss of dopaminergic neurons of the substantia nigra pars compacta, with the pathological hallmark being intracel­lular aggregates of α-synuclein, in the form of Lewy bodies and Lewy neurites. Several processes have been implicated in PD, including mitochondrial dysfunc­tion, defective protein clearance mechanisms, and neuroinflammation, but the way in which these factors interact remains incompletely understood.