Tar DNA Binding Protein, TDP43 or TARDBP was originally identified as a transcriptional repressor that binds to chromosomally integrated TAR DNA and represses HIV-1 transcription. It was also reported to regulate alternate splicing of the CFTR gene and the apoA-II gene.
Later it was discovered that hyper-phosphorylated, ubiquitinated and cleaved form of TARDBP, known as pathologic TDP43, is the major disease protein in ubiquitin-positive, tau-, and alpha-synuclein-negative frontotemporal dementia (FTLD-U) and in Amyotrophic lateral sclerosis (ALS). Elevated levels of the TDP-43 protein have also been identified in individuals diagnosed with chronic traumatic encephalopathy, a condition that often mimics ALS and that has been associated with athletes who have experienced multiple concussions and other types of head injury.
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