DJ-1, a Parkinson’s disease-associated gene, prevents excessive inflammation through interaction with SHP-1
Kim, Jong-hyeon; Choi, Dong-joo; Kim, Jun; Joe, Eun-hye
Department of Pharmacology
DJ-1, PARK7, is a Parkinson’s disease (PD)-associated gene whose mutation has been identified in an early onset autosomal-recessive PD. Inflammation occurred in response to tissue damage to protect hosts against pathogens. However, excessive inflammatory responses are also detrimental to hosts, leading to aggravation of the injury. Particularly, brain inflammation has been considered a risk factor of PD. The results in this study showed that DJ-1 is a negative regulator of inflammation. Microglia and/or astrocytes prepared from DJ-1 knockout (KO) mice compared to that from wild-type (WT) mice significantly increased STAT1 phosphorylation and expression of iNOS, COX-2 and TNF-a in response to IFN-g. Accordingly, DJ-1 overexpression in DJ-1 KO astrocytes reduced STAT1 phosphorylation. DJ-1 appears to directly bind to both SHP-1 and STAT1, and assist their interaction. Therefore, in the absence of DJ-1, the interaction between STAT1 and SHP-1 reduced, which causes enhanced STAT1 phosphorylation in KO cells. These findings suggest that DJ-1 prevents excessive inflammation through the interaction with STAT1 and SHP-1. Thus, loss of DJ-1 may increase the risk of PD through the enhancement of brain inflammation.
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