title: α-Synuclein levels affect autophagosome numbers in vivo and modulate Huntington disease pathology.
abstract: Huntington and Parkinson diseases (HD and PD) are two major neurodegenerative disorders pathologically characterized by the accumulation of the aggregate-prone proteins mutant huntingtin (in HD) and α-synuclein (in PD). Mutant huntingtin is an autophagy substrate and autophagy modulators affect HD pathology both in vitro and in vivo. In vitro, α-synuclein levels are able to modulate autophagy: α-synuclein overexpression inhibits autophagy, whereas downregulation promotes autophagy. Here, we review our recent studies showing that α-synuclein levels modulate mutant huntingtin toxicity in mouse models. This phenotypic modification is accompanied by the in vivo modulation of autophagosome numbers in mouse brains from both control and HD mice expressing different levels of α-synuclein.
authors.affiliation: MRC Mammalian Genetics Unit, Harwell, Oxfordshire, UK.
authors.forename: Silvia
authors.initials: S
authors.lastname: Corrochano
authors.forename: Maurizio
authors.initials: M
authors.lastname: Renna
authors.forename: Cristina
authors.initials: C
authors.lastname: Tomas-Zapico
authors.forename: Steve D M
authors.initials: SD
authors.lastname: Brown
authors.forename: Jose J
authors.initials: JJ
authors.lastname: Lucas
authors.forename: David C
authors.initials: DC
authors.lastname: Rubinsztein
authors.forename: Abraham
authors.initials: A
authors.lastname: Acevedo-Arozena
mesh_terms: D000818:Animals; D001343:Autophagy; D004195:Disease Models, Animal; D004331:Drosophila melanogaster / Q000378:metabolism; D006801:Humans; D006816:Huntington Disease / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D050505:Mutant Proteins / Q000378:metabolism; D010588:Phagosomes / Q000378:metabolism*; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; D050505:Mutant Proteins; D051844:alpha-Synuclein