Neuroprotective effect of undecylenic acid extracted from Ricinus communis L. through inhibition of μ-calpain.

European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences
Eunyoung LeeYoungjoo Kwon

Abstract

The key neuropathological features of Alzheimer's disease are abnormal deposition of Aβ plaques and insoluble Aβ peptides in extracellular brain and intracellular neurofibril tangles induced by abnormal tau hyperphosphorylation. μ-Calpain is one of the factors that bridge these Aβ- and hyperphosphorylated tau-mediated pathological pathways. Undecylenic acid (UDA), a naturally occurring unsaturated fatty acid, was discovered as a μ-calpain inhibitor by screening a chemical library using a substrate specific μ-calpain assay method. UDA inhibited Aβ oligomerization and Aβ fibrillation and reversed Aβ-induced neuronal cell death. In addition, UDA scavenged ROS and reversed the levels of proapoptotic proteins induced by ROS in SH-SY5Y cells. UDA inhibited μ-calpain activity with better potency than the known peptide-like μ-calpain inhibitor, MDL28170, in SH-SY5Y and HEK293T cells transfected with the catalytic subunit of μ-calpain. These results suggest that UDA is a novel non-peptide-like μ-calpain inhibitor with good cell permeability and potent neuroprotective effect.

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Citations

Dec 19, 2012·Biochimica Et Biophysica Acta·Eunyoung LeeYoungjoo Kwon
Nov 18, 2014·Expert Opinion on Therapeutic Patents·Isaac O Donkor
May 20, 2020·Enzyme and Microbial Technology·Mohamed Chafik BourkaibIsabelle Chevalot
Mar 19, 2021·ChemMedChem·Loïc LeclercqAndreea-Ruxandra Schmitzer

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