TAILIEUCHUNG - Báo cáo Y học: Amyloid-fibril formation Proposed mechanisms and relevance to conformational disease

The phenomenon of the transformation of proteins into amyloid-fibrils is of interest, firstly, because it is closely connected to the so-called conformational diseases, many of which are hitherto incurable, and secondly, because it remains to be explained in physical terms (energetically and structurally). The process leads to fibrous aggregates in the form of extracellular amyloid plaques, neuro-fibrillary tangles and other intracytoplasmic or intranuclear inclusions. | Eur. J. Biochem. 269 3362-3371 2002 FEBS 2002 doi REVIEW ARTICLE Amyloid-fibril formation Proposed mechanisms and relevance to conformational disease Eva Zerovnik Department of Biochemistry and Molecular Biology Jozef Stefan Institute Ljubljana Slovenia The phenomenon of the transformation of proteins into amyloid-fibrils is of interest firstly because it is closely connected to the so-called conformational diseases many of which are hitherto incurable and secondly because it remains to be explained in physical terms energetically and structurally . The process leads to fibrous aggregates in the form of extracellular amyloid plaques neuro-fibrillary tangles and other intracytoplasmic or intranuclear inclusions. In this review basic principles common to the field of amyloid fibril formation and conformational disease are underlined. Existing models for the mechanism need to be tested by experiment. The kinetic and energetic bases of the process are reviewed. The main controversial issue remains the coexistence of more than one protein conformation. The possible role of oligomeric intermediates and of domainswapping is also discussed. Mechanisms for cellular defence and novel therapies are considered. Keywords amyloid fibrils conformational disease domain swapping kinetics mechanism of fibrillogenesis. Protein folding is important for cellular events ranging from transport accepting and transmitting signals regulation at the gene and RNA levels cell adhesion changes in cytoskeleton metabolic reactions involving various enzymes etc. An active protein conformation is needed for successful cell functioning and therefore important in maintaining health. Several types of disease have been found where protein misfolding and conformational change are the main causes of the appearance and progression of disease 1 . A list of conformational diseases together with their associated protein component s is shown in Table 1 2 . In some cases more .

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