title: FET proteins in frontotemporal dementia and amyotrophic lateral sclerosis.
abstract: Mutations in the fused in sarcoma gene (FUS) cause amyotrophic lateral sclerosis (ALS) with TDP-43-negative, FUS-positive pathology. FUS is also the pathological protein in most tau/TDP-43-negative subtypes of frontotemporal lobar degeneration (FTLD-FUS). FUS, together with Ewing's sarcoma protein (EWS) and TATA-binding protein associated factor 15 (TAF15), make up the FET family of DNA/RNA binding proteins that share functional homology and have the potential to interact. We recently investigated the role of the other FET proteins in the clinicopathological spectrum of FUS-opathies. In all FTLD-FUS subtypes, FUS-positive pathology was also labeled for TAF15 and EWS and cells with inclusions showed a reduction in the normal nuclear staining of all FET proteins. In contrast, in cases of ALS-FUS, TAF15 and EWS remained localized to the nucleus and did not label FUS-positive inclusions. Cell culture models replicated the human diseases. These findings indicate that ALS-FUS and FTLD-FUS have different pathomechanisms and add TAF15 and EWS to the growing list of RNA-binding proteins involved in neurodegeneration. This article is part of a Special Issue entitled: RNA-Binding Proteins.
authors.affiliation: Department of Pathology, Vancouver General Hospital, 855 West 12th Avenue, Vancouver, BC, Canada V5Z 1M9. ian.mackenzie@vch.ca
authors.forename: Ian R A
authors.initials: IR
authors.lastname: Mackenzie
authors.forename: Manuela
authors.initials: M
authors.lastname: Neumann
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D057174:Frontotemporal Lobar Degeneration / Q000235:genetics*; D006801:Humans; D002479:Inclusion Bodies / Q000235:genetics / Q000378:metabolism; D034802:RNA-Binding Protein EWS / Q000235:genetics; D034702:RNA-Binding Protein FUS / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D035381:TATA-Binding Protein Associated Factors / Q000235:genetics / Q000378:metabolism; D057177:TDP-43 Proteinopathies / Q000235:genetics; D016875:tau Proteins / Q000235:genetics
chemical_list: D034802:RNA-Binding Protein EWS; D034702:RNA-Binding Protein FUS; D016601:RNA-Binding Proteins; C102041:TAF15 protein, human; D035381:TATA-Binding Protein Associated Factors; D016875:tau Proteins