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: Ian R A Mackenzie, Manuela Neumann
• Journal: Brain research (Brain Res) Vol. 1462 Pg. 40-3 (Jun 26 2012) ISSN: 1872-6240 [Electronic] Netherlands
• PMID: 22261247 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2011 Elsevier B.V. All rights reserved.

Chemical References

• RNA-Binding Protein EWS
• RNA-Binding Protein FUS
• RNA-Binding Proteins
• TAF15 protein, human
• TATA-Binding Protein Associated Factors
• tau Proteins

Topics

• Amyotrophic Lateral Sclerosis (genetics)
• Frontotemporal Lobar Degeneration (genetics)
• Humans
• Inclusion Bodies (genetics, metabolism)
• RNA-Binding Protein EWS (genetics)
• RNA-Binding Protein FUS (genetics, metabolism)
• RNA-Binding Proteins (metabolism)
• TATA-Binding Protein Associated Factors (genetics, metabolism)
• TDP-43 Proteinopathies (genetics)
• tau Proteins (genetics)