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Membrane cholesterol interferes with neuronal apoptosis induced by soluble oligomers but not fibrils of the amyloid‐β peptide
Author(s) -
Sponne Isabelle,
Fifre Alexandre,
Kriem Badreddine,
Koziel Violette,
Bihain Bernard,
Oster Thierry,
Olivier Jean-Luc,
Pillot Thierry
Publication year - 2004
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.03-0372fje
Subject(s) - peptide , liposome , cholesterol , membrane , chemistry , fibril , apoptosis , p3 peptide , microbiology and biotechnology , amyloid (mycology) , neurodegeneration , biochemistry , biophysics , alzheimer's disease , amyloid precursor protein , biology , medicine , disease , inorganic chemistry
Neuronal cell death in Alzheimer's disease (AD) is partly induced by the interaction of the amyloid‐β peptide (Aβ) with the plasma membrane of target cells. Accordingly, recent studies have suggested that cholesterol, an important component of membranes that controls their physical properties and functions, plays a critical role in neurodegenerative diseases. We report here that the enrichment of the neuronal plasma membrane with cholesterol protects cortical neurons from apoptosis induced by soluble oligomers of the Aβ(1,40) peptide. Conversely, cholesterol depletion using cyclodextrin renders cells more vulnerable to the cytotoxic effects of the Aβ‐soluble oligomers. Increasing the cholesterol content of small unilamellar liposomes also decreases Aβ‐dependent liposome fusion. We clearly demonstrate that cholesterol protection is specific to the soluble conformation of Aβ, because we observed no protective effects on cortical neurons treated by amyloid fibrils of the Aβ(1‐40) peptide. This may provide a new opportunity for the development of an effective AD therapy as well as elucidate the impact of the cholesterol level during AD development.