TDP-43 pathology in polyglutamine diseases: with reference to amyotrphic lateral sclerosis.

Abstract

A nuclear protein, transactivation response (TAR) DNA binding protein 43 kDa (TDP-43), is the major component of neuronal cytoplasmic inclusions (NCIs) in frontotemporal lobar degeneration with ubiquitin inclusions (FTLD-U) and sporadic amyotrophic lateral sclerosis (SALS). While initially thought to be relatively specific to FTLD-U and ALS, TDP-43 pathology has now been detected in a number of other neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. In such tauopathies and α-synucleinopathies, occurrence of TDP-43-positive neuronal cytoplasmic inclusions may be associated with other distinct molecular pathologic processes primarily involving their own pathological proteins, tau and α-synuclein, respectively (secondary TDP-43 proteinopathies). On the other hand, in several polyglutamine (polyQ) diseases, TDP-43 appears to play an important pathomechanistic role. Interestingly, intermediate-length polyQ expansions (27-33 Qs) in ataxin 2, the causative gene of spinocerebellar ataxia type 2, have recently been reported to be a genetic risk factor for SALS. Here, with a review of the literature, we discuss the relationship between ALS and polyQ diseases from the viewpoint of TDP-43 neuropathology.

DOI: 10.1111/neup.12053

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@article{Toyoshima2014TDP43PI, title={TDP-43 pathology in polyglutamine diseases: with reference to amyotrphic lateral sclerosis.}, author={Yasuko Toyoshima and Hitoshi Takahashi}, journal={Neuropathology : official journal of the Japanese Society of Neuropathology}, year={2014}, volume={34 1}, pages={77-82} }