The role of ubiquitinated TDP-43 in amyotrophic lateral sclerosis

Deposition of intracellular ubiquitin inclusion in motor neurons is one of the leading pathogenic mechanisms of amyotrophic lateral sclerosis (ALS). The transactive response DNA binding protein-43 (TDP-43) is the main component of intracellular ubiquitin inclusion bodies in pathological deposits. TDP-43 is mainly distributed in the nucleus of neurons, and participates in nuclear RNA transcription, alternative splicing and mRNA stability regulation. The tardbp, as a coding gene, provides instructions for making TDP-43. After post-translational modification, the pathological TDP-43 induces pathological deposition in cells and is associated with neurodegenerative diseases, which is similar to tau in Alzheimer’s disease and alpha-synuclein in Parkinson’s disease. The pathogenic tardbp mutation can affect the localization of reverse transcription in the cell. This review summarizes the mechanisms underlying the pathogenesis of ALS by ubiquitination of TDP-43 protein