TARDBP (TAR DNA-binding protein 43, TDP-43) is a DNA and RNA-binding transcriptional repressor that regulates transcription and splicing. TARDBP is thought to be involved in microRNA biogenesis, apoptosis and cell division, and it can also repress HIV-1 transcription by binding to the HIV-1 long terminal repeat. It promotes CFTR exon 9 skipping, and the resulting aberrant splicing is associated with pathological features typical of cystic fibrosis. TARDBP binds to the mRNA of the neurofilament NEFL in spinal motor neurons, and it may be involved in regulating RNA transport, translation and stability in neurons in hippocampal dendrites. A pathogenic form of TARDBP plays a major role in frontotemporal dementia (FTLD-TDP) and amyotrophic lateral sclerosis (ALS). Furthermore, dysfunctional or upregulated TARDBP is found in Alzheimer’s disease and in cases of chronic traumatic encephalopathy. In immunohistochemistry, TARDBP has high nuclear positivity in all tissues.
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