TDP-43 and FUS in amyotrophic lateral sclerosis and frontotemporal dementia

Ian R A Mackenzie, Rosa V Rademakers, Manuela Neumann

Research output: Contribution to journalArticle

490 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)995-1007
Number of pages13
JournalThe Lancet Neurology
Volume9
Issue number10
DOIs
StatePublished - Oct 2010

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Frontotemporal Lobar Degeneration
Frontotemporal Dementia
RNA-Binding Proteins
Amyotrophic Lateral Sclerosis
DNA-Binding Proteins
Neurodegenerative Diseases
Proteins
Biomarkers
RNA
Frontotemporal Dementia With Motor Neuron Disease
Therapeutics
Protein Aggregates

ASJC Scopus subject areas

  • Clinical Neurology
  • Medicine(all)

Cite this

TDP-43 and FUS in amyotrophic lateral sclerosis and frontotemporal dementia. / Mackenzie, Ian R A; Rademakers, Rosa V; Neumann, Manuela.

In: The Lancet Neurology, Vol. 9, No. 10, 10.2010, p. 995-1007.

Research output: Contribution to journalArticle

Mackenzie, Ian R A ; Rademakers, Rosa V ; Neumann, Manuela. / TDP-43 and FUS in amyotrophic lateral sclerosis and frontotemporal dementia. In: The Lancet Neurology. 2010 ; Vol. 9, No. 10. pp. 995-1007.
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