title: Molecular genetics and biomarkers of polyglutamine diseases.
abstract: Polyglutamine diseases are hereditary neurodegenerative disorders caused by an abnormal expansion of a trinucleotide CAG repeat, which encodes a polyglutamine tract. To date, nine polyglutamine diseases are known: Huntington's disease (HD), spinal and bulbar muscular atrophy (SBMA), dentatorubral-pallidoluysian atrophy (DRPLA) and six forms of spinocerebellar ataxia (SCA). The diseases are inherited in an autosomal dominant fashion except for SBMA, which shows an X-linked pattern of inheritance. Although the causative gene varies with each disorder, polyglutamine diseases share salient genetic features as well as molecular pathogenesis. CAG repeat size correlates well with the age of onset in each disease, shows both somatic and germline instability, and has a strong tendency to further expand in successive generations. Aggregation of the mutant protein followed by the disruption of cellular functions, such as transcription and axonal transport, has been implicated in the etiology of neurodegeneration in polyglutamine diseases. Although animal studies have provided promising therapeutic strategies for polyglutamine diseases, it remains difficult to translate these disease-modifying therapies to the clinic. To optimize "proof of concept", the process for testing candidate therapies in humans, it is of importance to identify biomarkers which can be used as surrogate endpoints in clinical trials for polyglutamine diseases.
authors.affiliation: Institute for Advanced Research, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan. ka2no@med.nagoya-u.ac.jp
authors.forename: Masahisa
authors.initials: M
authors.lastname: Katsuno
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Banno
authors.forename: Keisuke
authors.initials: K
authors.lastname: Suzuki
authors.forename: Yu
authors.initials: Y
authors.lastname: Takeuchi
authors.forename: Motoshi
authors.initials: M
authors.lastname: Kawashima
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Tanaka
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Adachi
authors.forename: Gen
authors.initials: G
authors.lastname: Sobue
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D020271:Heredodegenerative Disorders, Nervous System / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy*; D006801:Humans; D008954:Models, Biological; D008967:Molecular Biology; D010455:Peptides / Q000235:genetics*; D019680:Trinucleotide Repeat Expansion
chemical_list: D015415:Biomarkers; D010455:Peptides; C097188:polyglutamine