title: 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.affiliation: Department of Pathology, Brain Research Institute, University of Niigata, Niigata, Japan.
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Toyoshima
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Takahashi
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000473:pathology*; D004268:DNA-Binding Proteins / Q000032:analysis*; D006801:Humans; D006816:Huntington Disease / Q000473:pathology; D002479:Inclusion Bodies / Q000473:pathology; D017827:Machado-Joseph Disease / Q000473:pathology; D010455:Peptides; D016601:RNA-Binding Proteins / Q000032:analysis; D020754:Spinocerebellar Ataxias / Q000473:pathology
chemical_list: D004268:DNA-Binding Proteins; D010455:Peptides; D016601:RNA-Binding Proteins; C097188:polyglutamine
keywords: RNA-binding protein; TDP-43; amyotrophic lateral sclerosis; polyglutamine disease; stress granules