title: Potential Modes of Intercellular α-Synuclein Transmission.
abstract: Intracellular aggregates of the α-synuclein protein result in cell loss and dysfunction in Parkinson's disease and atypical Parkinsonism, such as multiple system atrophy and dementia with Lewy bodies. Each of these neurodegenerative conditions, known collectively as α-synucleinopathies, may be characterized by a different suite of molecular triggers that initiate pathogenesis. The mechanisms whereby α-synuclein aggregates mediate cytotoxicity also remain to be fully elucidated. However, recent studies have implicated the cell-to-cell spread of α-synuclein as the major mode of disease propagation between brain regions during disease progression. Here, we review the current evidence for different modes of α-synuclein cellular release, movement and uptake, including exocytosis, exosomes, tunneling nanotubes, glymphatic flow and endocytosis. A more detailed understanding of the major modes by which α-synuclein pathology spreads throughout the brain may provide new targets for therapies that halt the progression of disease.
authors.affiliation: Menzies Health Institute Queensland, Griffith University, Gold Coast 4222, Australia. dario.valdinocci@griffithuni.edu.au.
authors.forename: Dario
authors.initials: D
authors.lastname: Valdinocci
authors.affiliation: Department of Biomedical Sciences, Faculty of Medical and Health Sciences, Macquarie University, Sydney 2109, Australia. rowan.radford@students.mq.edu.au.
authors.forename: Rowan A W
authors.initials: RA
authors.lastname: Radford
authors.affiliation: Menzies Health Institute Queensland, Griffith University, Gold Coast 4222, Australia. suemaye.siow@griffithuni.edu.au.
authors.forename: Sue Maye
authors.initials: SM
authors.lastname: Siow
authors.affiliation: Department of Biomedical Sciences, Faculty of Medical and Health Sciences, Macquarie University, Sydney 2109, Australia. roger.chung@mq.edu.au.
authors.forename: Roger S
authors.initials: RS
authors.lastname: Chung
authors.affiliation: Menzies Health Institute Queensland, Griffith University, Gold Coast 4222, Australia. d.pountney@griffith.edu.au.
authors.forename: Dean L
authors.initials: DL
authors.lastname: Pountney
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D002450:Cell Communication; D055354:Exosomes / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism*; D016631:Lewy Bodies / Q000378:metabolism; D020961:Lewy Body Disease / Q000378:metabolism / Q000473:pathology; D017628:Microglia / Q000378:metabolism; D008954:Models, Biological; D019578:Multiple System Atrophy / Q000378:metabolism / Q000473:pathology; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology; D066263:Protein Aggregation, Pathological; D011485:Protein Binding; D021381:Protein Transport; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D051844:alpha-Synuclein
keywords: Parkinson’s disease; dementia with Lewy bodies; exosome; gliosis; glymphatic; multiple system atrophy; tunneling nanotube; α-synuclein