title: Polyglutamine disease: recent advances in the neuropathology of dentatorubral-pallidoluysian atrophy.
abstract: Polyglutamine diseases are hereditary neurodegenerative disorders that are caused by the expansion of a CAG repeat in the causative genes. They comprise at least nine disorders, including DRPLA, HD, and Machado-Joseph disease. Initially, the discovery of neuronal intranuclear inclusions (NIIs) in human brains and in a murine model of HD provided a plausible hypothesis that the expression of expanded polyglutamine stretches leads to NII formation, resulting in neuronal cell death in selective brain regions characteristic to each disease. Recent studies, however, suggest that nuclear dysfunction, especially transcriptional abnormalities caused by the diffuse intranuclear accumulation of mutant proteins, plays a pivotal role in the development and progression of clinical symptoms. Polyglutamine diseases have a similarity with neuronal storage disease, and this pathological process might become a target for the establishment of an effective therapy for these diseases.
authors.affiliation: Department of Pathology, Brain Research Institute, Niigata University, Japan. nori@bri.niigata-u.ac.jp
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Yamada
authors.forename: Mitsuteru
authors.initials: M
authors.lastname: Shimohata
authors.forename: Toshiya
authors.initials: T
authors.lastname: Sato
authors.forename: Shoji
authors.initials: S
authors.lastname: Tsuji
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Takahashi
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D016923:Cell Death / Q000502:physiology; D004195:Disease Models, Animal; D020271:Heredodegenerative Disorders, Nervous System / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D045586:Intranuclear Inclusion Bodies / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D020191:Myoclonic Epilepsies, Progressive / Q000378:metabolism / Q000473:pathology*; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010455:Peptides / Q000378:metabolism*; D019680:Trinucleotide Repeat Expansion
chemical_list: D010455:Peptides; C097188:polyglutamine