title: TFEB: Pathogenic role and therapeutic target in Parkinson disease.
abstract: Parkinson disease (PD) is characterized by the progressive loss of nigral dopamine neurons and the presence of accumulations containing the disease-causing protein SNCA/α-synuclein. Here we review our recent findings describing how SNCA impairs the function of the master regulator of the autophagy-lysosomal pathway (ALP), the transcription factor EB (TFEB), and that genetic or pharmacological stimulation of its activity promotes protection of dopamine neurons. These findings suggest that strategies aimed at enhancing autophagy-mediated degradation of SNCA may hold great promise for disease intervention in PD.
authors.affiliation: Department of Experimental Medical Sciences; Wallenberg Neuroscience Center; Lund University; Lund, Skane Sweden.
authors.forename: Mickael
authors.initials: M
authors.lastname: Decressac
authors.forename: Anders
authors.initials: A
authors.lastname: Björklund
mesh_terms: D000818:Animals; D001343:Autophagy; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000502:physiology*; D005260:Female; D006801:Humans; D008636:Mesencephalon / Q000473:pathology*; D009474:Neurons / Q000378:metabolism*; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D051844:alpha-Synuclein
keywords: MIR128; Parkinson disease; TFEB; alpha-synuclein; dopamine; macroautophagy; neurodegeneration; temsirolimus