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.

• Authors: Yasuko Toyoshima, Hitoshi Takahashi
• Journal: Neuropathology : official journal of the Japanese Society of Neuropathology (Neuropathology) Vol. 34 Issue 1 Pg. 77-82 (Feb 2014) ISSN: 1440-1789 [Electronic] Australia
• PMID: 23889603 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: © 2013 Japanese Society of Neuropathology.

Chemical References

• DNA-Binding Proteins
• Peptides
• RNA-Binding Proteins
• polyglutamine

Topics

• Amyotrophic Lateral Sclerosis (pathology)
• DNA-Binding Proteins (analysis)
• Humans
• Huntington Disease (pathology)
• Inclusion Bodies (pathology)
• Machado-Joseph Disease (pathology)
• Peptides
• RNA-Binding Proteins (analysis)
• Spinocerebellar Ataxias (pathology)