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A rescue factor abolishing neuronal cell death by a wide spectrum of familial Alzheimer's disease genes and Aβ

  1. Ikuo Nishimoto†**
  1. †Departments of Pharmacology and Neurosciences, KEIO University School of Medicine, 160-8582 Tokyo, Japan; ‡Department of Neurology, 951-8122 Nagoya University School of Medicine, Nagoya, 466-0065 Japan; §Department of Neurology, Brain Research Institute, Niigata University School of Medicine, Niigata, 951-8122 Japan; Pole Biologie Cellulaire et Moleculaire, Institut Européen de Chimie et Biologie, Ecole Polytechnique, Avenue Pey Berland, F-33402 Talence Cedex, France; and ‖Department of Medicine, University of Tokai School of Medicine, Kanagawa, 259-1100 Japan

  1. Communicated by Tadamitsu Kishimoto, Osaka University, Osaka, Japan (received for review January 25, 2001)

Abstract

Through functional expression screening, we identified a gene, designated Humanin (HN) cDNA, which encodes a short polypeptide and abolishes death of neuronal cells caused by multiple different types of familial Alzheimer's disease genes and by Aβ amyloid, without effect on death by Q79 or superoxide dismutase-1 mutants. Transfected HN cDNA was transcribed to the corresponding polypeptide and then was secreted into the cultured medium. The rescue action clearly depended on the primary structure of HN. This polypeptide would serve as a molecular clue for the development of new therapeutics for Alzheimer's disease targeting neuroprotection.

Footnotes

    • ↵* Y.H. and T.N. contributed equally to this work.

    • ↵** To whom reprint requests should be addressed. E-mail: nisimoto{at}mc.med.keio.ac.jp.

    • Data deposition: The sequence reported in this paper has been deposited in the GenBank database (accession no. YA029066).

  • Abbreviations

    AD,
    Alzheimer's disease;
    FAD,
    familial AD;
    APP,
    amyloid precursor protein;
    PS,
    Presenilin;
    HN,
    Humanin;
    pHN,
    a plasmid encoding HN cDNA;
    s,
    synthetic;
    EcD,
    ecdysone;
    CM,
    cultured medium;
    sHNA,
    sHN with C8A;
    sHNG,
    synthetic S14G HN;
    SOD1,
    superoxide dismutase-1;
    CN,
    catalytically negative;
    DT,
    death-trap;
    HNR,
    L9R mutant of HN;
    EcR,
    ecdysone receptor;
    F11/EcR,
    F11 cells stably overexpressing EcR
    • Received January 25, 2001.
    • Accepted March 19, 2001.

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