Cited by 2,732Amyotrophic Lateral Sclerosis ResearchAlzheimer's disease research and treatmentsGenetic Neurodegenerative Diseases

TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis

Arai, Tetsuaki, Hasegawa, Masato, Akiyama, Haruhiko, Ikeda, Kenji, Nonaka, Takashi, Mori, Hiroshi, Mann, David, Tsuchiya, Kuniaki +3 more·2006·Biochemical and Biophysical Research Communications

Abstract

Ubiquitin-positive tau-negative neuronal cytoplasmic inclusions and dystrophic neurites are common pathological features in frontotemporal lobar degeneration (FTLD) with or without symptoms of motor neuron disease and in amyotrophic lateral sclerosis (ALS). Using biochemical and immunohistochemical analyses, we have identified a TAR DNA-binding protein of 43 kDa (TDP-43), a nuclear factor that functions in regulating transcription and alternative splicing, as a component of these structures in FTLD. Furthermore, skein-like inclusions, neuronal intranuclear inclusions, and glial inclusions in the spinal cord of ALS patients are also positive for TDP-43. Dephosphorylation treatment of the sarkosyl insoluble fraction has shown that abnormal phosphorylation takes place in accumulated TDP-43. The common occurrence of intracellular accumulations of TDP-43 supports the hypothesis that these disorders represent a clinicopathological entity of a single disease, and suggests that they can be newly classified as a proteinopathy of TDP-43.

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Crossref · 10.1016/j.bbrc.2006.10.093

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  • Biochemical and histopathologic examination of frontotemporal cortex and spinal cord in sALS patients reveals that ubiquitin-positive inclusions contain TARDBP.

    “biochemical and histopathologic examination of frontotemporal cortex and spinal cord in sALS patients reveals that ubiquitin-positive inclusions contain TARDBP [274,275]”

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Authors
Arai, T., Hasegawa, M., Akiyama, H., Ikeda, K., Nonaka, T., Mori, H., Mann, D., Tsuchiya, K., Yoshida, M., Hashizume, Y., & Oda, T.
Affiliations
  • Tokyo Institute of Psychiatry (JP)
  • Osaka City University (JP)
  • University of Manchester (GB)
  • Tokyo Metropolitan Matsuzawa Hospital (JP)
  • Aichi Medical University (JP)
Corresponding author
  • Arai, Tetsuaki
  • Hasegawa, Masato
Venue
Biochemical and Biophysical Research Communications
Publisher
Elsevier BV
Published
2006-12
Volume
351
Issue
3
Pages
602-611
ISSN
0006-291X (ISSN-L)
OpenAlex
W2031964319
Cited by
2,732
References
53
Citations by year
2026: 122 · 2025: 181 · 2024: 182 · 2023: 168 · 2022: 181 · 2021: 191 · 2020: 177 · 2019: 133 · 2018: 153 · 2017: 124 · 2016: 132 · 2015: 94 · 2014: 106 · 2013: 136 · 2012: 134
FWCI
57.53
Type
journal article
Language
en
Open access
closed
Locations
  • Biochemical and Biophysical Research Communications (publishedVersion)
  • PubMed (publishedVersion)
  • Research Explorer (The University of Manchester) (publishedVersion)
Topics
  • Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
Keywords
TDP-43, frontotemporal lobar degeneration, amyotrophic lateral sclerosis, dystrophic neurites, neuronal intranuclear inclusions, glial inclusions, TDP-43 phosphorylation, proteinopathies, motor neuron disease, neurodegeneration
MeSH terms
Aged, Aged, 80 and over, Amyotrophic Lateral Sclerosis, Brain, Inclusion Bodies, Dementia, DNA-Binding Proteins, Female, Humans, Male, Middle Aged, Tissue Distribution, tau Proteins, Ubiquitin

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