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J Korean Neurol Assoc. 2011;29(1):1-8.
- The Pathogenetic Role of TAR DNA Binding Protein (TDP-43) in
Amyotrophic Lateral Sclerosis and Frontotemporal Dementia
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Sa-Yoon Kang
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Department of Neurology, Jeju National University College of Medicine, Jeju, Korea
- 근위축측삭경화증과 전두측두엽치매에서 TAR DNA
Binding Protein (TDP-43)의 병인론적 역할
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제주대학교 의학전문대학원 신경과학교실
- Abstract
- The recent identification of the transactive response DNA binding protein with a molecular weight of 43 kDa (TDP-43) as
the major pathological protein, in both amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with
ubiquitin positive inclusions (FTLD-U), provides the new insight into understanding disease processes. The
pathogenesis of both diseases is unclear, although they are related by having some overlap of symptoms and now by the
shared histopathology of TDP-43 deposition. The number of degenerative diseases associated with TDP-43 has
increased, leading to the new designation "TDP-43 proteinopathy". TDP-43 is a highly conserved protein ubiquitously
expressed in many tissues including the central nervous system where it is present in neuronal and glial nuclei and to a
lesser extent in the cytoplasm. Currently, TDP-43 has been implicated in regulating gene transcription and alternative
splicing, in addition to maintaining mRNA stability. However, we still need to investigate the effects of posttranslational
modifications of TDP-43, including phosphorylation, ubiquitination, and cleavage, on its regulation of various cellular
processes. We review recently published studies of TDP-43 and its relationship to human disease with a special focus on
ALS and FTLD-U. We conclude that the TDP-43 proteinopathies represent a novel class of neurodegenerative disorders
and both ALS and FTLD-U are closely related conditions linked to similar mechanism of neurodegeneration. Key Words: Amyotrophic lateral sclerosis, Frontotemporal lobar degeneration, Neurodegeneration, TAR DNA binding
protein-43 (TDP-43)
Keywords :
- 초록
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