TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis
- Department of Psychogeriatrics, Tokyo Institute of Psychiatry 2-1-8 Kamikitazawa, Setagaya-ku, Tokyo 156-8585 (Japan)
- Department of Molecular Neurobiology, Tokyo Institute of Psychiatry 2-1-8 Kamikitazawa, Setagaya-ku, Tokyo 156-8585 (Japan)
- Zikei hospital 100-2 Urayasuhonmachi, Okayama-shi, Okayama 702-8508 (Japan)
- Department of Neuroscience, Osaka City University School of Medicine, 1-4-3 Asahimachi, Abenoku, Osaka 545-8585 (Japan)
- Greater Manchester Neurosciences Centre, University of Manchester, Hope Hospital, Salford M6 8HD (United Kingdom)
- Department of Laboratory Medicine and Pathology, Tokyo Metropolitan Matsuzawa Hospital, 2-1-1 Kamikitazawa, Setagaya-ku, Tokyo 156-0057 (Japan)
- Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University, 21 Karimata, Yazako, Nagakute-cho, Aichi-gun, Aichi 480-1195 (Japan)
- Department of Neuropsychiatry, National Shimofusa Mental Hospital, Chiba 266-0007 (Japan)
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.
- OSTI ID:
- 20857924
- Journal Information:
- Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 3 Vol. 351; ISSN 0006-291X; ISSN BBRCA9
- Country of Publication:
- United States
- Language:
- English
Similar Records
The N-terminus of TDP-43 promotes its oligomerization and enhances DNA binding affinity
Imbalance of mitochondrial dynamics in Drosophila models of amyotrophic lateral sclerosis