title: Pathophysiology of synuclein aggregation in Lewy body disease.
abstract: We provide an overview of synaptic pathology in dementia with Lewy bodies (DLB) and related neurodegenerative disorders that are characterised by intraneuronal accumulation of alpha-synuclein aggregates. The review addresses the clinico-neuropathological correlates of synaptic pathology in Lewy body disease, and concentrates on: altered alpha-synuclein metabolism, mechanisms leading to alpha-synuclein fibril formation (self-polymerisation, alpha-synuclein mutations and post-translational modifications) and how these influence the axonal transport and synaptic network in ageing and disease process. Understanding the mechanisms leading to intraneuronal alpha-synuclein accumulation are crucial for the development of novel therapies for treatment of Lewy body disease.
authors.affiliation: Institute for Ageing and Health, University of Newcastle, Newcastle General Hospital, Westgate Road, Newcastle upon Tyne NE4 6BE, UK. Elizabeta.Mukaetova-Ladinska@ncl.ac.uk
authors.forename: Elizabeta B
authors.initials: EB
authors.lastname: Mukaetova-Ladinska
authors.forename: Ian G
authors.initials: IG
authors.lastname: McKeith
mesh_terms: D000375:Aging / Q000378:metabolism / Q000473:pathology; D001369:Axons / Q000378:metabolism / Q000473:pathology; D001692:Biological Transport; D006801:Humans; D020961:Lewy Body Disease / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D046912:Multiprotein Complexes / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism / Q000473:pathology; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D046912:Multiprotein Complexes; D051844:alpha-Synuclein