Original Article Pathological accumulation of atrophin-1 in dentatorubralpallidoluysian atrophy
Yasuyo Suzuki, Ikuru Yazawa
Laboratory of Research Resources, Research Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, Aichi, Japan
Received March 29, 2011; accepted April 21, 2011; Epub April 25, 2011; published April 30, 2011
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 neurodegeneration. 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. (IJCEP1103009).
Address all correspondence to: Ikuru Yazawa, MD, PhD Laboratory of Research Resources Research Institute for Longevity Sciences National Center for Geriatrics and Gerontology 35 Gengo, Morioka-cho, Obu-shi Aichi 474-7511, Japan. Tel: +81-562-46-2311, Fax: +81-562-46-8319 E-mail: email@example.com