PRKN and Parkinsonism: Apart from mutations, parkin E3 ligase activity can be inactivated both in vitro and in vivo by S-nitrosylation,7 oxidative stress8 and dopaminergic stress.9 The combination of these stresses plus heterozygous parkin mutations can also lead to earlier manifestations of parkinsonism.10 AR-JP symptomatology resembles sporadic PD, with loss of neuromelanin positive (NM+) catecholaminergic neurons in the SNpc and locus coeruleus.