Vincent BM~Rhodes KJ, 2018

Pubmed ID 30517862
Title Inhibiting Stearoyl-CoA Desaturase Ameliorates α-Synuclein Cytotoxicity.
Authors Benjamin M Vincent, Daniel F Tardiff, Jeff S Piotrowski, Rebecca Aron, Matthew C Lucas, Chee Yeun Chung, Helene Bacherman, YiQun Chen, Michelle Pires, Radha Subramaniam, Dimple B Doshi, Heather Sadlish, Waseem K Raja, Eric J Solís, Vikram Khurana, Bertrand Le Bourdonnec, Robert H Scannevin, Kenneth J Rhodes
Abstract The lack of disease-modifying treatments for neurodegenerative disease stems in part from our rudimentary understanding of disease mechanisms and the paucity of targets for therapeutic intervention. Here we used an integrated discovery paradigm to identify a new therapeutic target for diseases caused by α-synuclein (α-syn), a small lipid-binding protein that misfolds and aggregates in Parkinson's disease and other disorders. Using unbiased phenotypic screening, we identified a series of compounds that were cytoprotective against α-syn-mediated toxicity by inhibiting the highly conserved enzyme stearoyl-CoA desaturase (SCD). Critically, reducing the levels of unsaturated membrane lipids by inhibiting SCD reduced α-syn toxicity in human induced pluripotent stem cell (iPSC) neuronal models. Taken together, these findings suggest that inhibition of fatty acid desaturation has potential as a therapeutic approach for the treatment of Parkinson's disease and other synucleinopathies.
Citation Cell Rep 2018; 25:2742-2754.e31

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Curation history

Tested strains

Feb. 18, 2019 Not relevant.

Data

Feb. 18, 2019 Not relevant.