[Component of ubiquitin-positive inclusions in ALS].
TAR DNA-binding protein of 43 kDa (TDP-43), a heterogeneous nuclear ribonucleoprotein that functions in regulating transcription and alternative splicing, was identified as a component of ubiquitin-positive tau-negative cytoplasimic inclusions in frontotemporal lobar degeneration (FTLD-U), and subsequently of ubiquitin-positive skein-like inclusions in amyotrophic lateral sclerosis (ALS). Dephosphorylation treatment of sarkosyl-insoluble fractions have suggested that abnormal phosphorylation takes place in the deposited 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. This article reviews the ubiquitin-positive inclusions in ALS and the recent discovery of TDP-43 in tau-negative inclusions in FTLD-U and ALS. We also discuss the biological implications of these findings for the pathogenesis of ALS.
Hasegawa
Masato
M
Department of Molecular Neur-obiology, Tokyo Institute of Psychiatry, 2-1-8 Kamikitazawa, Setagaya-ku, Tokyo 156-8585, Japan.
Arai
Tetsuaki
T
D000690:Amyotrophic Lateral Sclerosis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005625:Frontal Lobe / Q000166:cytology / Q000473:pathology; D006801:Humans; D002479:Inclusion Bodies / Q000378:metabolism*; D009046:Motor Neurons / Q000166:cytology / Q000473:pathology; D009410:Nerve Degeneration; D010766:Phosphorylation; D013702:Temporal Lobe / Q000166:cytology / Q000473:pathology; D025801:Ubiquitin / Q000378:metabolism*
D004268:DNA-Binding Proteins; D025801:Ubiquitin