Mechanisms of neuroprotection by a novel rescue factor humanin from Swedish mutant amyloid precursor protein

Biochem Biophys Res Commun. 2001 May 4;283(2):460-8. doi: 10.1006/bbrc.2001.4765.

Abstract

We report a novel gene, designated Humanin (HN) cDNA, that suppresses neuronal cell death by K595N/M596L-APP (NL-APP), a mutant causing familial Alzheimer's disease (FAD), termed Swedish mutant. Transfection of neuronal cells with HN cDNA or treatment with the coding HN polypeptide abrogated cytotoxicity by NL-APP. HN suppressed neurotoxicity by Abeta1-43 in the absence of N2 supplement, but could not inhibit Abeta secretion from NL-APP. HN could also protect neuronal cells from death by NL-APP lacking the 41st and 42nd residues of the Abeta region. Therefore, HN suppressed neuronal cell death by NL-APP not through inhibition of Abeta42 secretion, but with two targets for its inhibitory action: (i) the intracellular toxic mechanism directly triggered by NL-APP and (ii) neurotoxicity by Abeta. HN will contribute to the development of curative therapy of AD, especially as a novel reagent that could mechanistically supplement Abeta-production inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / genetics*
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology
  • Alzheimer Disease / therapy
  • Amino Acid Sequence
  • Amyloid beta-Peptides / metabolism
  • Amyloid beta-Protein Precursor / genetics*
  • Base Sequence
  • Cell Death / drug effects
  • DNA, Complementary / genetics
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Molecular Sequence Data
  • Mutation*
  • Neurons / drug effects
  • Neurons / pathology
  • Neuroprotective Agents / pharmacology*
  • Proteins / genetics
  • Proteins / pharmacology*
  • Sweden
  • Transfection

Substances

  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • DNA, Complementary
  • Intracellular Signaling Peptides and Proteins
  • Neuroprotective Agents
  • Proteins
  • humanin