Antioxidants inhibit neuronal toxicity in Parkinson's disease-linked LRRK2

作者：Angeles Dario C; Ho Patrick; Dymock Brian W; Lim Kah Leong; Zhou Zhi Dong; Tan Eng King^*

来源：Annals of Clinical and Translational Neurology, 2016, 3(4): 288-294.

DOI：10.1002/acn3.282

Mutations in leucine-rich repeat kinase-2 are the most common cause of familial Parkinson's disease. The prevalent G2019S mutation increase oxidative, kinase and toxic activity and inhibit endogenous peroxidases. We initially screened a library of 84 antioxidants and identified seven phenolic compounds that inhibited kinase activity on leucine-rich repeat kinase-2 substrates. The representative antioxidants (piceatannol, thymoquinone, and esculetin) with strong kinase inhibitor activity, reduced loss in dopaminergic neurons, oxidative dysfunction, and locomotor defects in G2019S-expressing neuronal and Drosophila models compared to weak inhibitors. We provide proof of principle that natural antioxidants with dual antioxidant and kinase inhibitor properties could be useful for leucine-rich repeat kinase-2-linked Parkinson's disease.

• 出版日期2016-4