title: Neuroprotective effect of undecylenic acid extracted from Ricinus communis L. through inhibition of μ-calpain.
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.
authors.affiliation: College of Pharmacy, Division of Life & Pharmaceutical Sciences, Ewha Womans University, Seoul 120-750, Republic of Korea.
authors.forename: Eunyoung
authors.initials: E
authors.lastname: Lee
authors.forename: Ji-Eun
authors.initials: JE
authors.lastname: Eom
authors.forename: Hye-Lin
authors.initials: HL
authors.lastname: Kim
authors.forename: Da-Hye
authors.initials: DH
authors.lastname: Kang
authors.forename: Kyu-Yeon
authors.initials: KY
authors.lastname: Jun
authors.forename: Duk Sang
authors.initials: DS
authors.lastname: Jung
authors.forename: Youngjoo
authors.initials: Y
authors.lastname: Kwon
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors*; D002154:Calpain / Q000037:antagonists & inhibitors*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects*; D003627:Data Interpretation, Statistical; D004151:Dipeptides / Q000494:pharmacology; D055808:Drug Discovery; D057809:HEK293 Cells; D006801:Humans; D018625:Microscopy, Atomic Force; D009474:Neurons / Q000187:drug effects / Q000201:enzymology; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D010539:Permeability / Q000187:drug effects; D058225:Plaque, Amyloid / Q000188:drug therapy; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors; D012278:Ricinus / Q000737:chemistry; D054852:Small Molecule Libraries; D014476:Undecylenic Acids / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D016229:Amyloid beta-Peptides; D004151:Dipeptides; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D054852:Small Molecule Libraries; D014476:Undecylenic Acids; D002154:Calpain; C449002:mu-calpain; C484806:CAPN1 protein, human; C058076:calpain inhibitor III