title: TDP-43 and FUS in amyotrophic lateral sclerosis and frontotemporal dementia.
abstract: Abnormal intracellular protein aggregates comprise a key characteristic in most neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The seminal discoveries of accumulation of TDP-43 in most cases of ALS and the most frequent form of FTD, frontotemporal lobar degeneration with ubiquitinated inclusions, followed by identification of FUS as the novel pathological protein in a small subset of patients with ALS and various FTD subtypes provide clear evidence that these disorders are related. The creation of a novel molecular classification of ALS and FTD based on the identity of the predominant protein abnormality has, therefore, been possible. The striking functional and structural similarities of TDP-43 and FUS, which are both DNA/RNA binding proteins, imply that abnormal RNA metabolism is a pivotal event, but the mechanisms leading to TDP-43 and FUS accumulation and the resulting neurodegeneration are currently unknown. Nonetheless, TDP-43 and FUS are promising candidates for the development of novel biomarker assays and targeted therapies.
authors.affiliation: Department of Pathology and Laboratory Medicine, Vancouver General Hospital, Vancouver, BC, Canada.
authors.forename: Ian Ra
authors.initials: IR
authors.lastname: Mackenzie
authors.forename: Rosa
authors.initials: R
authors.lastname: Rademakers
authors.forename: Manuela
authors.initials: M
authors.lastname: Neumann
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000175:diagnosis* / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D057180:Frontotemporal Dementia / Q000175:diagnosis* / Q000235:genetics* / Q000378:metabolism; D005819:Genetic Markers / Q000235:genetics / Q000502:physiology; D006801:Humans; D009154:Mutation / Q000235:genetics; D034702:RNA-Binding Protein FUS / Q000737:chemistry / Q000235:genetics* / Q000502:physiology
chemical_list: D004268:DNA-Binding Proteins; D005819:Genetic Markers; D034702:RNA-Binding Protein FUS