Parkinson's disease (PD)-associated Pink1 and Parkin proteins are believed to function in a common pathway controlling mitochondrial clearance and trafficking.
Parkinson's Disease (PD) related genes PINK1, a protein kinase [1], and Parkin, an E3 ubiquitin ligase [2], operate within the same pathway [3-5], which controls, via specific elimination of dysfunctional mitochondria, the quality of the organelle network [6].
Parkinson's disease (PD)-associated E3 ubiquitin ligase Parkin is enriched at glutamatergic synapses, where it ubiquitinates multiple substrates, suggesting that its mutation/loss-of-function could contribute to the etiology of PD by disrupting excitatory neurotransmission.
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.
Parkin protein, whose mutants are the cause of Parkinson disease type 2 (PARK2), has been mechanistically linked to the regulation of apoptosis and the turnover of damaged mitochondria.
PARK2 mutations are frequently associated with Parkinson's disease, but structural alterations have also been described in patients with neurodevelopmental disorders (NDD), suggesting a pathological effect ubiquitous to neurodevelopmental and neurodegenerative brain processes.
PARKIN overexpression in human mesenchymal stromal cells from Wharton's jelly suppresses 6-hydroxydopamine-induced apoptosis: Potential therapeutic strategy in Parkinson's disease.
A single nucleotide polymorphism in the parkin promoter (rs9347683, -258T/G) has been reported to be associated with PD and shown to functionally affect gene transcription in luciferase reporter assays.
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.
A wide variety of mutations in the parkin gene are responsible for autosomal recessive parkinsonism in Europe. French Parkinson's Disease Genetics Study Group and the European Consortium on Genetic Susceptibility in Parkinson's Disease.
According to our data, the genetic variation at the PARKIN gene (including promoter polymorphisms) did not contribute to the risk of developing PD in the general population.
All of the changes observed in the brains of these Drosophila models of PD, in which mitochondrial ligases MUL1 and PARKIN do not function, may explain the mechanisms of some neurological and behavioural symptoms of PD.
Although muscle dysfunction is noted in Parkinson's disease, little is known about the involvement of PARKIN in the muscle phenotype of Parkinson's disease.