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- Title
Antioxidants inhibit neuronal toxicity in Parkinson's disease-linked LRRK2.
- Authors
Angeles, Dario C.; Ho, Patrick; Dymock, Brian W.; Lim, Kah‐Leong; Zhou, Zhi‐Dong; Tan, Eng‐King
- Abstract
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.
- Subjects
KINASES; PARKINSON'S disease; PEROXIDASE; ANTIOXIDANTS; KINASE inhibitors
- Publication
Annals of Clinical & Translational Neurology, 2016, Vol 3, Issue 4, p288
- ISSN
2328-9503
- Publication type
Article
- DOI
10.1002/acn3.282