tailieunhanh - Báo cáo khoa học: Interactions between metals and a-synuclein ) function or artefact?

a-synuclein is one of a family of proteins whose function remains unknown. This protein has become linked to a number of neurodegenera-tive disease although its potential causative role in these diseases remains mysterious. In diseases such as Parkinson’s disease and Lewy body demen-tias, a-synuclein becomes deposited in aggregates termed Lewy bodies. | FEBS Journal MINIREVIEW Interactions between metals and a-synuclein - function or artefact David R. Brown Department of Biology and Biochemistry University of Bath UK Keywords amyloid copper Lewy body Parkinson s disease Correspondence D. R. Brown Department of Biology and Biochemistry University of Bath Claverton Down Bath BA2 7AY UK Fax 44 1225 386779 Tel 44 1225 383133 E-mail bssdrb@ Received 9 March 2007 revised 1 May 2007 accepted 7 May 2007 doi a-synuclein is one of a family of proteins whose function remains unknown. This protein has become linked to a number of neurodegenera-tive disease although its potential causative role in these diseases remains mysterious. In diseases such as Parkinson s disease and Lewy body dementias a-synuclein becomes deposited in aggregates termed Lewy bodies. Also some inherited forms of Parkinson s diseases are linked to mutations in the gene for a-synuclein. Studies have mostly focussed on what causes the aggregation of the protein but like many amyloidogenic proteins associated with a neurodegenerative disorder this protein has now been suggested to bind copper. This finding is currently controversial. This review examines the evidence that a-synuclein is a copper binding protein and discusses whether this has any significance in determining the function of the protein or whether copper binding is at all necessary for aggregation. Introduction Advances in research in recent years have linked many neurodegenerative diseases to specific proteins that undergo either abnormal conformational changes or whose metabolism is somehow modified. Links between Alzheimer s disease AD and amyloid-P AP Creutzfeldt-Jakob disease and prions are well documented 1 . In recent years another protein has been discovered that is related to a variety of neuro-degenerative disorders. This protein originally termed the nonamyloid component precursor was identified in the plaques of AD and was later termed .

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