Parkinson's Disease
Parkinson's disease (PD) is the most common degenerative movement disorder, which was initially described by Dr James Parkinson in the 19th century. PD affects more than 1.5% of the population over 65 years old. The clinical symptoms of PD include bradykinesia, resting tremor, rigidity and postural instability, with psychiatric and cognitive presentations in some patients. Pathologically, PD is characterized by the progressive death of midbrain dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc) and the formation of abnormal intracellular protein aggregates, named Lewy bodies (LBs) and Lewy neurites (LNs), in the remaining DA neurons. α-synuclein (α-syn) is enriched in LBs and LNs. Interestingly, only familial cases with dominant genetic mutations in α-syn and LRRK2 develop typical PD pathology, including SNc DA neuronal loss and LB/LN formation. Therefore, understanding the pathophysiological functions of α-syn and LRRK2 may provide critical molecular insights into the pathogenesis of PD, which is required to develop any mechanism-based therapeutic strategies to ameliorate this devastating illness.