Mutations in PARK7 are a rare cause of familial recessive Parkinson's disease (PD), but growing evidence suggests involvement of DJ-1 in idiopathic PD.
Mutations the in human DJ-1 (hDJ-1) gene are associated with early-onset autosomal recessive forms of Parkinson's disease (PD). hDJ-1/parkinsonism associated deglycase (PARK7) is a cytoprotective multi-functional protein that contains a conserved cysteine-protease domain.
DJ-1 has been identified as a gene responsible for recessive familial Parkinson's disease (familial Parkinsonism), which is caused by a mutation in the PARK7 locus.
One such protein is Parkinson protein 7, which has been implicated in Parkinson's disease, yet not associated with epilepsy, Alzheimers disease, or autism spectrum disorder.
Mutations in seven genes are robustly associated with autosomal dominant (SNCA, LRRK2, EIF4G1, VPS35) or recessive (parkin/PARK2, PINK1, DJ1/PARK7) Parkinson's disease (PD) or parkinsonism.
Pathogenic autosomal recessive mutations in the DJ-1 (Park7) or the PTEN-induced putative kinase 1 (Pink1 or PARK6) genes are associated with familial Parkinson's disease (PD).
To date, MJFF has initiated and funded the generation of 30 different models, which include transgenic or knockout models of PD-relevant genes such as Park1 (also known as Park4 and SNCA), Park8 (LRRK2), Park7 (DJ-1), Park6 (PINK1), Park2 (Parkin), VPS35, EiF4G1 and GBA.
Data mining for single-nucleotide polymorphisms (SNP), reportedly associated with breast cancer in genome-wide association study (GWAS) that localize to chromosomes bearing known Parkinson's disease predisposition loci: PARK7, PINK1 (chromosome 1); SNCA (chromosome 4); PARK2 (chromosome 6); and LRRK2 (chromosome 12), was carried out.
Loss-of-function mutations in the gene encoding the multifunctional protein, DJ-1, have been implicated in the pathogenesis of early-onset familial Parkinson's disease (PD), suggesting that DJ-1 may act as a neuroprotectant for dopaminergic (DA) neurons.