The parkin gene on chromosome 6q and loci on chromosome 1p35-36 and 1p36 are responsible for some cases of autosomal recessive early-onset parkinsonism, but they do not appear to influence susceptibility or variability of age at onset for idiopathic PD.
Parkin, a RING-between-RING-type E3 ubiquitin ligase associated with Parkinson's disease, has a wide neuroprotective activity, preventing cell death in various stress paradigms.
Parkin functions as a multipurpose E3 ubiquitin ligase, and Parkin loss of function is associated with both sporadic and familial Parkinson's disease (PD).
Our study aimed at conducting screening for mutations in PARK2 in patients with a sporadic form of PD to clarify the role of PARK2 in the development of PD.
A subset of familial PD is linked to mutations in PARK2 and PINK1, which lead to dysfunctional mitochondria-related proteins Parkin and PINK1, suggesting that pathways implicated in these monogenic forms could play a more general role in PD.
Parkin gene mutation testing was performed in young onset PD (diagnosed <50 years old) to identify three groups: Parkin homozygous or compound heterozygote mutation carriers, Parkin single heterozygote mutation carriers, and non-carriers of Parkin mutations.
The clinical relevance of our findings is substantiated by the discovery of homozygous PARKIN (<i>PARK2</i>) p.S65N mutations in two unrelated patients with PD.
Furthermore, we demonstrate that Nedd4, another E3 ubiquitin ligase that may have a role in PD, is functionally related to Sep4 and could be involved in regulating Sep4 subcellular localization/trafficking.
From 102 patients, 40 with early-onset PD (<45 years at symptomatic onset) were selected for clinical assessment and parkin gene molecular analysis for duplications/deletions and point mutations.
Parkin is a ligase involved in ubiquitin-proteasome pathway and mutations in the parkin gene are the most common cause of recessive familial Parkinson's disease.
In the present report we have screened a cohort of Parkinson disease patients (n = 57) and healthy controls (n = 51) from Nigeria for mutations in the genes PRKN, LRRK2 and ATXN3.
Genes which have been implicated in autosomal-recessive PD include PARK2 which codes for parkin, an E3 ubiquitin ligase that participates in a variety of cellular activities.
The turnover of damaged mitochondria by mitophagy is initiated by the Parkinson disease-linked genes PRKN and PINK1, and we recently investigated the role that interorganellar contact sites between the endoplasmic reticulum (ER) and the outer mitochondrial membrane (OMM) play in this pathway.