Pathophysiology of synuclein aggregation in Lewy body disease.
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.
Mukaetova-Ladinska
Elizabeta B
EB
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
McKeith
Ian G
IG
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*
D046912:Multiprotein Complexes; D051844:alpha-Synuclein