Abstract
Alzheimer's and Parkinson's diseases are associated with the formation in the brain of amyloid fibrils from beta-amyloid and alpha-synuclein proteins, respectively. It is likely that oligomeric fibrillization intermediates (protofibrils), rather than the fibrils themselves, are pathogenic, but the mechanism by which they cause neuronal death remains a mystery. We show here that mutant amyloid proteins associated with familial Alzheimer's and Parkinson's diseases form morphologically indistinguishable annular protofibrils that resemble a class of pore-forming bacterial toxins, suggesting that inappropriate membrane permeabilization might be the cause of cell dysfunction and even cell death in amyloid diseases.
MeSH terms
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Alzheimer Disease / genetics*
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Alzheimer Disease / metabolism
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Alzheimer Disease / pathology
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Amyloid beta-Peptides / chemistry*
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Amyloid beta-Peptides / genetics*
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Amyloid beta-Peptides / metabolism
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Amyloid beta-Peptides / toxicity
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Cell Membrane Permeability / drug effects
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Chromatography, Gel
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Circular Dichroism
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Humans
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Models, Biological
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Molecular Weight
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Mutation / genetics
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Nerve Tissue Proteins / chemistry*
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Nerve Tissue Proteins / genetics*
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Nerve Tissue Proteins / metabolism
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Nerve Tissue Proteins / toxicity
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Parkinson Disease / genetics*
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Parkinson Disease / metabolism
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Parkinson Disease / pathology
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Plaque, Amyloid / genetics
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Plaque, Amyloid / metabolism
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Plaque, Amyloid / pathology
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Porins / chemistry*
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Porins / genetics*
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Porins / metabolism
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Porins / toxicity
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Protein Structure, Quaternary
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Protein Structure, Secondary
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Synucleins
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alpha-Synuclein
Substances
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Amyloid beta-Peptides
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Nerve Tissue Proteins
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Porins
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SNCA protein, human
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Synucleins
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alpha-Synuclein