TAILIEUCHUNG - Báo cáo khoa học: Biochemical and biophysical features of both oligomer⁄fibril and cell membrane in amyloid cytotoxicity

A great deal must still be learnt on the structural features of amyloid assemblies, particularly prefibrillar aggregates, and the relationship of the latter with amyloid cytotoxicity. Presently, it is recognized that the popula-tion of unstable, heterogeneous amyloid oligomers and protofibrils is mainly responsible for amyloid cytotoxicity. | MINIREVIEW Biochemical and biophysical features of both oligomer fibril and cell membrane in amyloid cytotoxicity Massimo Stefani Department of BiochemicalSciences and Research Centre on the Molecular Basis of Neurodegeneration University of Florence Italy Keywords amyloid amyloid cytotoxicity amyloid diseases amyloid oligomers cell membranes Correspondence M. Stefani Department of Biochemical Sciences Viale Morgagni 50 50134 Florence Italy Fax 39 0554598905 Tel 39 0554598307 E-mail stefani@ Website http unifi scibio pers Received 21 January 2010 revised 8 September 2010 accepted 13 September 2010 doi A great deal must still be learnt on the structural features of amyloid assemblies particularly prefibrillar aggregates and the relationship of the latter with amyloid cytotoxicity. Presently it is recognized that the population of unstable heterogeneous amyloid oligomers and protofibrils is mainly responsible for amyloid cytotoxicity. Conversely mature fibrils are considered stable harmless reservoirs of molecular species devoid of toxicity in the polymerized state. This view has been modified by recent reports showing that mature fibrils grown at different conditions can display different structural features and stabilities possibly leading them to undergo disassembly with the leak of toxic oligomers. Fibril polymorphism is paralleled by oligomer polymorphism and both can be traced back to amyloid growth from differently destabilized monomers with distinct structural features at differing conditions. Recent research has started to unravel oligomer structural and biophysical features and the relationship between the latter and oligomer cytotoxicity. These data have led to the proposal that together both oligomer and membrane physical features determine the extent of oligomer-membrane interaction with the resulting disruption of membrane integrity and cell impairment. Such a view can help to .

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