title: Synaptic failure and α-synuclein.
abstract: Although the physiological function of α-synuclein is not fully understood, it has been suggested to primarily localize to the presynaptic terminals of mature neurons, where it fulfills roles in synaptic function and plasticity. Based on current knowledge, α-synuclein (αSYN) is thought to be involved in maintaining neurotransmitter homeostasis by regulating synaptic vesicle fusion, clustering, and trafficking between the reserve and ready-releasable pools, as well as interacting with neurotransmitter membrane transporters. In this review, we focus on evidence proposing synapses as the main site of αSYN pathology and its propagation in Parkinson's disease and dementia with Lewy bodies, which belong to a group of neurodegenerative diseases known as α-synucleinopathies. We provide an overview of the evidence supporting presynaptic dysfunction as the primary event in the pathogenesis of these conditions.
authors.affiliation: Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Laura
authors.initials: L
authors.lastname: Calo
authors.affiliation: Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Michal
authors.initials: M
authors.lastname: Wegrzynowicz
authors.affiliation: Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Jessica
authors.initials: J
authors.lastname: Santivañez-Perez
authors.affiliation: Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Maria
authors.initials: M
authors.lastname: Grazia Spillantini
mesh_terms: D006801:Humans; D020961:Lewy Body Disease / Q000378:metabolism* / Q000473:pathology; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology; D013569:Synapses / Q000378:metabolism* / Q000473:pathology; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D051844:alpha-Synuclein
keywords: synapse; α-synuclein; α-synucleopathies