title: Impulse control disorder, lysosomal malfunction and ATP13A2 insufficiency in Parkinsonism.
abstract: Lysosomal transport of cargos in neurons is essential for neuronal proteostasis, transmission and functional motors and behaviours. Lysosomal malfunction including storage disorders is involved in the pathogenesis of Parkinson's disease (PD). Given the unclear molecular mechanisms of diverse defects in PD phenotypes, especially behavioural deficits, this mini review explores the cellular contexts of PD impulse control disorders and the molecular aspects of lysosomal cross-membrane transports. Focuses are paid to trace metal involvements in α-synuclein assembly in Lewy bodies, the functions and molecular interactions of ATP13A2 as ATPase transporters in lysosomal membranes for cross-membrane trafficking and lysosomal homeostasis, and our current understandings of the neural circuits in ICD. Erroneously polarized distributions of cargos such as metals and lipids on each side of lysosomal membranes triggered by gene mutations and deregulated expression of ATP13A2 may thus instigate sensing protein structural changes such as aggregations, organelle degeneration, and specific neuronal ageing and death in Parkinsonism.
authors.affiliation: School of Medicine, Institute of Ageing Research, Hangzhou Normal University, Hangzhou, Zhejiang Province, China.|Department of Molecular and Translational Science, Faculty of Medicine, Hudson Institute of Medical Research, Monash University, Clayton, VIC, Australia.|Department of Immunology, Faculty of Medicine, Central Clinical School, Monash University, Prahran, VIC, Australia.
authors.forename: Jun-Ping
authors.initials: JP
authors.lastname: Liu
authors.affiliation: School of Medicine, Institute of Ageing Research, Hangzhou Normal University, Hangzhou, Zhejiang Province, China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Li
authors.affiliation: School of Medicine, Institute of Ageing Research, Hangzhou Normal University, Hangzhou, Zhejiang Province, China.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Lu
authors.affiliation: School of Medicine, Institute of Ageing Research, Hangzhou Normal University, Hangzhou, Zhejiang Province, China.
authors.forename: Lihui
authors.initials: L
authors.lastname: Wang
authors.affiliation: School of Medicine, Institute of Ageing Research, Hangzhou Normal University, Hangzhou, Zhejiang Province, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
mesh_terms: D000818:Animals; D007174:Disruptive, Impulse Control, and Conduct Disorders / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D016631:Lewy Bodies / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism*; D008345:Manganese / Q000378:metabolism; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D010300:Parkinson Disease / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D021381:Protein Transport; D006180:Proton-Translocating ATPases / Q000235:genetics / Q000378:metabolism*; D051844:alpha-Synuclein / Q000378:metabolism
chemical_list: C514983:ATP13A2 protein, human; C497604:SNCA protein, human; D051844:alpha-Synuclein; D008345:Manganese; D006180:Proton-Translocating ATPases
keywords: hypersexuality; impulse control disorder; lysosome transport; skin picking; trace metals; trichotillomania