[HTML][HTML] Amyloid pores from pathogenic mutations
Nature, 2002•nature.com
Alzheimer's and Parkinson's diseases are associated with the formation in the brain of
amyloid fibrils from β-amyloid and α-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 …
amyloid fibrils from β-amyloid and α-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 …
Abstract
Alzheimer's and Parkinson's diseases are associated with the formation in the brain of amyloid fibrils from β-amyloid and α-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.
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