Abstract：
:Parkinson's disease (PD) is a progressive neurodegenerative disorder that is primarily characterized by the degeneration of dopaminergic neurons in the nigrostriatal pathway. Loss-of-function mutations in the gene encoding PARK7/DJ-1 were identified in familial PD. Wild-type DJ-1 acts as an oxidative stress sensor in neural cells. Previously, we identified binding compounds of DJ-1, including UCP0045037/compound A, UCP0054278/compound B, and compound-23 (comp-23), by in silico virtual screening. These compounds prevented oxidative stress-induced dopaminergic neuronal death and restored locomotion defects in animal models of PD. In addition, these binding partners reduced infarct size in cerebral ischemia in rats. The neuroprotective effects of these compounds are lost in DJ-1-knockdown cells and DJ-1-knockout animal. These results suggest that these compounds interact with endogenous DJ-1 and then produce antioxidant and neuroprotective responses in both animal models for PD and cerebral ischemia in rats. This raises the possibility that interaction partners of DJ-1, such as UCP0045037, UCP0054278, and comp-23, may represent a novel dopaminergic neuroprotective drug for the treatment of PD.
journal_name
Adv Exp Med Bioljournal_title
Advances in experimental medicine and biologyauthors
Inden M,Yanagisawa D,Hijioka M,Ariga H,Kitamura Ydoi
10.1007/978-981-10-6583-5_12subject
Has Abstractpub_date
2017-01-01 00:00:00pages
187-202eissn
0065-2598issn
2214-8019journal_volume
1037pub_type
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