title: LAMP2A as a therapeutic target in Parkinson disease.
abstract: Abnormal aggregation of SNCA/?-synuclein plays a crucial role in Parkinson disease (PD) pathogenesis. SNCA levels determine its toxicity, and its accumulation, even to a small extent, may be a risk factor for neurodegeneration. One of the main pathways for SNCA degradation is chaperone-mediated autophagy (CMA), a selective form of autophagy, while aberrant SNCA may act as a CMA inhibitor. In the current punctum we summarize our recent data showing that induction of CMA, via overexpression of the protein controlling its rate-limiting step, the lysosomal receptor LAMP2A, effectively decreases SNCA levels and ameliorates SNCA-induced neurodegeneration, both in neuronal cell culture systems and in the rat brain. Such findings suggest that modulation of LAMP2A and, consequently, CMA, represents a viable therapeutic target for PD and other synucleinopathies where SNCA accumulation and aggregation plays a fundamental role.
authors.affiliation: Division of Basic Neurosciences; Biomedical Research Foundation of the Academy of Athens (BRFAA); Athens, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Xilouri
authors.forename: Oeystein Roed
authors.initials: OR
authors.lastname: Brekk
authors.forename: Deniz
authors.initials: D
authors.lastname: Kirik
authors.forename: Leonidas
authors.initials: L
authors.lastname: Stefanis
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D000229:Dependovirus / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D052119:Lysosomal-Associated Membrane Protein 2 / Q000378:metabolism*; D058990:Molecular Targeted Therapy; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism; D051381:Rats; D019076:Transgenes; D051844:alpha-Synuclein / Q000502:physiology
chemical_list: D052119:Lysosomal-Associated Membrane Protein 2; C497606:Snca protein, rat; D051844:alpha-Synuclein
keywords: LAMP2A; Parkinson disease; alpha-synuclein; chaperone-mediated autophagy; dopaminergic system; neurotoxicity; substantia nigra