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Title
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TDP-43 and FUS in amyotrophic lateral sclerosis and frontotemporal dementia
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Author
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Abstract
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| 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. |
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Language
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English
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Source (journal)
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The lancet neurology. - London
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Publication
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New york
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Elsevier science inc
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2010
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ISSN
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1474-4422
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DOI
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10.1016/S1474-4422(10)70195-2
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Volume/pages
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9
:10
(2010)
, p. 995-1007
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ISI
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000283616700014
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Full text (Publisher's DOI)
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