title: Pathological accumulation of atrophin-1 in dentatorubralpallidoluysian atrophy.
abstract: Dentatorubral-pallidoluysian atrophy (DRPLA) is caused by the expansion of polyglutamine (polyQ) in atrophin-1 (ATN1), also known as DRPLA protein. ATN1 is ubiquitously expressed in the central nervous system (CNS), although selective regions of CNS are degenerated in DRPLA, and this selective neuronal damage gives rise to the specific clinical features of DRPLA. Accumulation of mutant ATN1 that carries an expanded polyQ tract seems to be the primary cause of DRPLA neurodegeneration, but it is still unclear how the accumulation of ATN1 leads to neu-rodegeneration. Recently, cleaved fragments of ATN1 were shown to accumulate in the disease models and the brain tissues of patients with DRPLA. Furthermore, proteolytic processing of ATN1 may regulate the intracellular localization of ATN1 and its fragments. Therefore, proteolytic processing of ATN1 may provide clues to disease pathogenesis and hopefully aid in the determination of molecular targets for effective therapeutic approaches for DRPLA.
authors.affiliation: Laboratory of Research Resources, Research Institute for Longevity Sciences, National Center for Geriatrics and Gerontology Aichi, Japan.
authors.forename: Yasuyo
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Ikuru
authors.initials: I
authors.lastname: Yazawa
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D006801:Humans; D009154:Mutation; D020191:Myoclonic Epilepsies, Progressive / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D010641:Phenotype; D011499:Protein Processing, Post-Translational; D015854:Up-Regulation
chemical_list: D009419:Nerve Tissue Proteins; D010455:Peptides; C095278:atrophin-1; C097188:polyglutamine