Research Paper Volume 12, Issue 18 pp 18561—18570
Chetomin rescues pathogenic phenotype of LRRK2 mutation in drosophila
- 1 Department of Neurology, National Neuroscience Institute, Singapore General Hospital, Singapore 169856, Singapore
- 2 Department of Neurology, National Neuroscience Institute Singapore, Singapore 169857, Singapore
- 3 Department of Neurology, Singapore General Hospital Singapore 169856, Singapore
- 4 Neuroscience Behavioral Disorders Program, Duke-NUS School, Singapore 169857, Singapore
Received: May 21, 2020 Accepted: July 6, 2020 Published: September 24, 2020https://doi.org/10.18632/aging.103843
How to Cite
Copyright: © 2020 Chua et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Leucine-rich repeat kinase 2 (LRRK2) is a complex protein kinase involved in a diverse set of functions. Mutations in LRRK2 are a common cause of autosomal dominant familial Parkinson’s disease. Peroxiredoxin 2 (PRDX2) belongs to a family of anti-oxidants that protect cells from oxidative stress. Importantly, PRDX2 is a cytoplasmic protein, similar to Leucine-rich repeat kinase 2, which localizes predominantly in the cytosol. Here, we demonstrated that Leurice-rich repeat kinase 2 phosphorylates PRDX2 in Drosophila, leading to a loss of dopaminergic neurons, climbing ability and shortened lifespan. These pathogenic phenotypes in the LRRK2 Drosophila were rescued with transgenic expression of PRDX2. Chetomin, a PRDX2 mimic, belongs to a class of epidithio-diketopiperazine fungal secondary metabolites (containing a dithiol group that has hydrogen peroxide-reducing activity). As proof of principle, we demonstrated that Chetomin recapitulated the rescue in these mutant Drosophila. Our findings suggest that Chetomin can be a potential therapeutic compound in LRRK2 linked Parkinson’s disease.