title: From pathways to targets: understanding the mechanisms behind polyglutamine disease.
abstract: The history of polyglutamine diseases dates back approximately 20 years to the discovery of a polyglutamine repeat in the androgen receptor of SBMA followed by the identification of similar expansion mutations in Huntington's disease, SCA1, DRPLA, and the other spinocerebellar ataxias. This common molecular feature of polyglutamine diseases suggests shared mechanisms in disease pathology and neurodegeneration of disease specific brain regions. In this review, we discuss the main pathogenic pathways including proteolytic processing, nuclear shuttling and aggregation, mitochondrial dysfunction, and clearance of misfolded polyglutamine proteins and point out possible targets for treatment.
authors.affiliation: Institute of Medical Genetics and Applied Genomics, University of Tübingen, Calwerstraße 7, 72076 Tübingen, Germany ; Rare Disease Center, Calwerstraße 7, 72076 Tübingen, Germany.
authors.forename: Jonasz Jeremiasz
authors.initials: JJ
authors.lastname: Weber
authors.affiliation: Institute of Medical Genetics and Applied Genomics, University of Tübingen, Calwerstraße 7, 72076 Tübingen, Germany ; Rare Disease Center, Calwerstraße 7, 72076 Tübingen, Germany.
authors.forename: Anna Sergeevna
authors.initials: AS
authors.lastname: Sowa
authors.affiliation: Institute of Medical Genetics and Applied Genomics, University of Tübingen, Calwerstraße 7, 72076 Tübingen, Germany ; Rare Disease Center, Calwerstraße 7, 72076 Tübingen, Germany.
authors.forename: Tina
authors.identifier: 0000-0002-4833-8057
authors.initials: T
authors.lastname: Binder
authors.affiliation: Institute of Medical Genetics and Applied Genomics, University of Tübingen, Calwerstraße 7, 72076 Tübingen, Germany ; Rare Disease Center, Calwerstraße 7, 72076 Tübingen, Germany.
authors.forename: Jeannette
authors.identifier: 0000-0002-4973-0923
authors.initials: J
authors.lastname: Hübener
mesh_terms: D000818:Animals; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D009410:Nerve Degeneration / Q000473:pathology*; D010455:Peptides / Q000378:metabolism*; D066263:Protein Aggregation, Pathological; D059748:Proteolysis; D015398:Signal Transduction
chemical_list: D010455:Peptides; C097188:polyglutamine