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  • Title: Neurodegenerative disease: amyloid pores from pathogenic mutations.
    Author: Lashuel HA, Hartley D, Petre BM, Walz T, Lansbury PT.
    Journal: Nature; 2002 Jul 18; 418(6895):291. PubMed ID: 12124613.
    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.
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