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

Eunyoung Lee, Ji Eun Eom, Hye Lin Kim, Da Hye Kang, Kyu Yeon Jun, Duk Sang Jung, Youngjoo Kwon

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

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.

Original languageEnglish
Pages (from-to)17-25
Number of pages9
JournalEuropean Journal of Pharmaceutical Sciences
Volume46
Issue number1-2
DOIs
StatePublished - 12 May 2012

Keywords

  • Extraction of Ricinus communis L.
  • Tau hyperphosphorylation
  • Undecylenic acid
  • p25 Generation
  • μ-Calpain inhibitor

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