What causes TDP-43?
What causes TDP-43?
More recent studies using a variety of cultured cells have demonstrated that exposure to stress causes TDP-43 re-localization to stress granules (SGs) [42–47], cytoplasmic foci that represent both sites of translationally stalled RNAs as well as active sites of RNA regulation and sorting [48, 49].
What is fused in sarcoma?
Fused in sarcoma (FUS) is a nuclear DNA/RNA binding protein that regulates different steps of gene expression, including transcription, splicing and mRNA transport.
Where is TDP-43 found in ALS?
TDP-43 is usually located in the nucleus — the cellular compartment that houses DNA — where it is involved in DNA and RNA processing. In ALS, however, TDP-43 tends to accumulate in aggregates (clumps) outside of the nucleus in the cytoplasm.
What is the function of TDP 43?
TAR DNA binding protein 43 (TDP-43) is a versatile RNA/DNA binding protein involved in RNA-related metabolism. Hyper-phosphorylated and ubiquitinated TDP-43 deposits act as inclusion bodies in the brain and spinal cord of patients with the motor neuron diseases: amyotrophic lateral sclerosis (ALS) a …
What is the pathophysiology of TDP43?
TDP-43 is the pathological protein in ALS and FTLD-U One of the most characteristic neuropathological features of ALS is the presence of ubiquitin-immunoreactive (ub-ir) neuronal cytoplasmic inclusions (NCI) in the degenerating motor neurons [4].
How does TDP-43 become mislocalized in neurodegenerative diseases?
In neurodegenerative diseases, neuronal and glial TDP-43 becomes mislocalized to the cytoplasm, where it aggregates into stress granules and insoluble inclusion bodies. These inclusions occur in all people with FTD or ALS caused by mutations in C9ORF72, progranulin, valosin-containing protein, or TDP-43 itself,…
