Protein Information

ID 2921
Name DJ 1
Synonyms DJ 1; DJ1; Oncogene DJ1; PARK 7; PARK7; Protein DJ 1; RNA binding protein regulatory subunit; Oncogene DJ1s…

Compound Information

ID 1341
Name rotenone
CAS

Reference

PubMed Abstract RScore(About this table)
18331584 Liu F, Nguyen JL, Hulleman JD, Li L, Rochet JC: Mechanisms of DJ-1 neuroprotection in a cellular model of Parkinson's disease. J Neurochem. 2008 Apr 15.
Mitochondrial dysfunction, proteasome inhibition, and alpha-synuclein aggregation are thought to play important roles in the pathogenesis of Parkinson's disease (PD). Rare cases of early-onset PD have been linked to mutations in the gene encoding DJ-1, a protein with antioxidant and chaperone functions. In this study, we examined whether DJ-1 protects against various stresses involved in PD, and we investigated the underlying mechanisms. Expression of wild-type DJ-1 rescued primary dopaminergic neurons from toxicity elicited by rotenone, proteasome inhibitors, and mutant alpha-synuclein. Neurons with reduced levels of endogenous DJ-1 were sensitized to each of these insults, and DJ-1 mutants involved in familial PD exhibited decreased neuroprotective activity. DJ-1 alleviated rotenone toxicity by up-regulating total intracellular glutathione. In contrast, inhibition of alpha-synuclein toxicity by DJ-1 correlated with up-regulation of the stress-inducible form of Hsp70. RNA interference studies revealed that this increase in Hsp70 levels was necessary for DJ-1-mediated suppression of alpha-synuclein aggregation, but not toxicity. Our findings suggest that DJ-1 acts as a versatile pro-survival factor in dopaminergic neurons, activating different protective mechanisms in response to a diverse range of PD-related insults.
13(0,0,1,8)