Abstract
The transactivation response DNA binding protein (TDP-43) is an RNA-binding protein involved in the processing of hundreds to thousands of RNA transcripts. This protein becomes mislocalized to the cytoplasm and forms characteristic inclusions found in most cases of amyotrophic lateral sclerosis (ALS) and many cases of frontotemporal dementia. Rare mutations in the gene encoding TDP-43 also cause ALS. Herein, we briefly review the genetics, pathology, and molecular and cellular basis of ALS, with a particular focus on TDP-43 and related TDP-43 proteinopathies. Dysfunctional TDP-43 can affect multiple cellular pathways, leading to cellular stress and neurodegeneration. Further elucidation of the normal and pathological role of TDP-43 may reveal strategies for the development of effective therapeutics.
Original language | English |
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Title of host publication | The Molecular and Cellular Basis of Neurodegenerative Diseases |
Subtitle of host publication | Underlying Mechanisms |
Publisher | Elsevier Inc. |
Pages | 99-115 |
Number of pages | 17 |
ISBN (Electronic) | 9780128113059 |
ISBN (Print) | 9780128113042 |
DOIs | |
Publication status | Published - 4 Apr 2018 |
Keywords
- Frontotemporal dementia
- Protein inclusions
- RNA processing
- Stress granules