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Int J Clin Exp Pathol 2011;4(4):378-384

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).

Keywords: Dentatorubral-pallidoluysian atrophy (DRPLA), atrophin-1 (ATN1), polyglutamine (polyQ) disease, neurodegeneration

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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