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Polyglutamine‐induced ion channels: a possible mechanism for the neurotoxicity of huntington and other CAG repeat diseases
Author(s) -
Hirakura Yutaka,
Azimov Rustam,
Azimova Rushania,
Kagan Bruce L.
Publication year - 2000
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/(sici)1097-4547(20000515)60:4<490::aid-jnr7>3.0.co;2-9
Subject(s) - neurotoxicity , ion channel , mechanism (biology) , anticipation (artificial intelligence) , trinucleotide repeat expansion , microbiology and biotechnology , pathogenesis , intracellular , huntington's disease , biology , chemistry , biophysics , genetics , disease , toxicity , medicine , gene , immunology , allele , philosophy , receptor , organic chemistry , epistemology , artificial intelligence , computer science
CAG repeats resulting in long polyglutamine tracts have been implicated in the pathogenesis of at least eight neurodegenerative diseases including Huntington. Expression of polyglutamine repeats is required for disease and increasing length of the repeats leads to earlier onset of illness (anticipation). Expression of polyglutamine repeats in cultured neurons leads to deposition of intracellular aggregates resembling those found in amyloid diseases, and to neurotoxicity. We report here that polyglutamine can induce large (19–220 pS), long‐lived, (lifetime = 6 sec), non‐selective (P cation = P anion ) ion channels in planar phospholipid bilayer membranes, and that channel formation is enhanced by acidic pH. We propose that channel formation may be a mechanism of cellular toxicity in Huntington and other CAG repeat disease. J. Neurosci. Res. 4:490–494, 2000 © 2000 Wiley‐Liss, Inc.