title: The Contribution ofα-Synuclein Spreading to Parkinson's Disease Synaptopathy.
abstract: Synaptopathies are diseases with synapse defects as shared pathogenic features, encompassing neurodegenerative disorders such as Parkinson's disease (PD). In sporadic PD, the most common age-related neurodegenerative movement disorder, nigrostriatal dopaminergic deficits are responsible for the onset of motor symptoms that have been related toα-synuclein deposition at synaptic sites. Indeed,α-synuclein accumulation can impair synaptic dopamine release and induces the death of nigrostriatal neurons. While in physiological conditions the protein can interact with and modulate synaptic vesicle proteins and membranes, numerous experimental evidences have confirmed that its pathological aggregation can compromise correct neuronal functioning. In addition, recent findings indicate thatα-synuclein pathology spreads into the brain and can affect the peripheral autonomic and somatic nervous system. Indeed, monomeric, oligomeric, and fibrillaryα-synuclein can move from cell to cell and can trigger the aggregation of the endogenous protein in recipient neurons. This novel "prion-like" behavior could further contribute to synaptic failure in PD and other synucleinopathies. This review describes the major findings supporting the occurrence ofα-synuclein pathology propagation in PD and discusses how this phenomenon could induce or contribute to synaptic injury and degeneration.
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
authors.forename: Francesca
authors.identifier: 0000-0001-6569-9412
authors.initials: F
authors.lastname: Longhena
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
authors.forename: Gaia
authors.initials: G
authors.lastname: Faustini
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Missale
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy; IRCCS Fondazione Ospedale San Camillo (NHS-Italy), Venice Lido, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Pizzi
authors.affiliation: IRCCS Fondazione Ospedale San Camillo (NHS-Italy), Venice Lido, Italy.
authors.forename: PierFranco
authors.initials: P
authors.lastname: Spano
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
authors.forename: Arianna
authors.identifier: 0000-0002-9581-1919
authors.initials: A
authors.lastname: Bellucci
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D059290:Dopaminergic Neurons / Q000378:metabolism / Q000473:pathology; D006801:Humans; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D013569:Synapses / Q000378:metabolism* / Q000473:pathology* / Q000502:physiology; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D051844:alpha-Synuclein