TAR DNA-binding protein 43

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Protein TARDBP PDB 1wf0
TAR DNA-binding protein 43
Identifiers
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TAR DNA-binding protein 43 (TDP-43) is a protein that in humans is encoded by the TARDBP gene. TDP-43 is involved in various cellular processes, including transcription, RNA splicing, and mRNA stability. It is predominantly located in the nucleus but can also be found in the cytoplasm under certain conditions.

Function[edit | edit source]

TDP-43 is a highly conserved and ubiquitously expressed protein that binds to both DNA and RNA. It plays a crucial role in the regulation of gene expression by binding to specific sequences in the DNA and RNA. TDP-43 is involved in the processing of pre-mRNA and the regulation of mRNA stability and transport.

Clinical Significance[edit | edit source]

TDP-43 has been implicated in several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). In these diseases, TDP-43 is often found to be abnormally phosphorylated, ubiquitinated, and cleaved, leading to the formation of cytoplasmic inclusions. These inclusions are a hallmark of the pathology of these diseases.

Structure[edit | edit source]

TDP-43 contains two RNA recognition motifs (RRMs) that allow it to bind to RNA. It also has a glycine-rich C-terminal region that is involved in protein-protein interactions. The protein can form aggregates under pathological conditions, which are thought to contribute to the disease process in ALS and FTLD.

Research[edit | edit source]

Ongoing research is focused on understanding the exact mechanisms by which TDP-43 contributes to neurodegeneration. Studies are also exploring potential therapeutic strategies to prevent or reverse the pathological aggregation of TDP-43.

See Also[edit | edit source]

References[edit | edit source]

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Contributors: Prab R. Tumpati, MD