Parkinson's Signaling

Parkinson's disease (PD) is a neurodegenerative disorder associated with loss of dopaminergic neurons and the presence of intracytoplasmic-ubiquitinated inclusions (Lewy bodies) and neurites. Several genes are implicated in PD including alpha-synuclein, parkin, ubiquitin C-terminal hydrolase L1 (UCHL1) and PARK-3, -4 and -7.A major pathway that leads to PD involves aberrations in the ubiquitin-proteasome pathway. Some of the proteins involved: 1) Parkin - an E3-ubiquitin-protein ligase that ubiquitinates several proteins and targets them for proteasomal degradation, 2) Alpha-synuclein - abnormal aggreation of this protein is often seen in PD, 3) UCHL1 - mutations in this thiol protease could lead to aberrations in the proteolytic pathway and aggregation of proteins, 4) Parkin associated endothelin-like receptor (Pael-R), 5) Septin 5, 6) Synphilin-1.