Parkinson

Parkinson disease (PD) is a neurodegenerative disorder, whose clinical manifestations include resting tremor, muscular rigidity and akinesia. PD is associated to the selective degeneration and death of dopaminergic neurons and is characterized by the deposition of abnormal protein aggregates called “Lewy bodies” in the surviving dopaminergic neurons. Alpha-synuclein is a major protein component of Lewy bodies and is found to be mutated or over-expressed in patients with PD. Other proteins that have been found to be mutated or over-expressed in PD are: Parkin, it is an E3 ubiquitin ligase that, in normal condition, ubiquitinates alpha-synuclein with its consequent proteasome-dependent degradation, mutations in Parkin gene lead to accumulation of alpha-synuclein; UCH-L1 is an Ubiquitin hydrolase that generates Ubiquitin monomers, necessary for the degradation of alpha-synuclein, mutant forms of UCH-L1 result in accumulation of alpha-synuclein; Mutations in DNAJC14 genes are associated with increased level of oxidative stress that predispose neurons to precipitate alpha-synuclein.