title: Structural studies of parkin and sacsin: Mitochondrial dynamics in neurodegenerative diseases.
abstract: Neurodegenerative diseases are prevalent, chronic diseases emanating from the dysfunction or death of neurons. The disrupted mitochondrial dynamics observed in a large number of neurodegenerative diseases suggests a common etiology with the possibility of therapies targeting multiple diseases. This review highlights the contributions of structural studies of disease-related proteins to the understanding of neurodegenerative disease pathogenesis and especially the cellular events leading to disruptions in mitochondrial dynamics and function. The examples used are parkin and sacsin, two proteins linked respectively to autosomal-recessive early-onset PD and autosomal-recessive spastic ataxia of Charlevoix-Saguenay. Structural studies of parkin and sacsin explain the pathogenicity of a large number of disease-associated mutations and reveal insights into their cellular functions related to mitochondrial dynamics.
authors.affiliation: Department of Biochemistry and Groupe de recherche axé sur la structure des protéines, McGill University, Montréal, Québec, Canada.
authors.forename: Xinlu
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Groupe de recherche axé sur la structure des protéines, McGill University, Montréal, Québec, Canada.
authors.forename: Kalle
authors.initials: K
authors.lastname: Gehring
mesh_terms: D006360:Heat-Shock Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D063154:Mitochondrial Dynamics / Q000502:physiology*; D008958:Models, Molecular; D009154:Mutation / Q000235:genetics; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D006360:Heat-Shock Proteins; C404403:SACS protein, human; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein
keywords: chaperone; mitochondria; mitophagy; parkin; sacsin