Progress in the role and mechanism of TDP-43

Background: TAR DNA-binding protein 43 kDa (TDP-43) has been shown to play an important role in the development of neurodegenerative diseases, but the mechanism is still under study. Methods: By utilizing “TDP43”, “disease”, and “mechanism” as the keywords, 200 related studies were retrieved and downloaded from Pubmed database, including 60 articles. We summarized the progress in understanding TDP-43 mechanism over the past two years, focusing on disease systems and classification of the upstream and downstream, including connection, improvement, and formation. Results: TDP-43, when abnormally aggregated, phosphorylated, or mislocalized, plays a key pathological role in neurodegenerative diseases. Additionally, its impact on normal reproductive cell formation, development, quantity, and activity, as well as insulin secretion and the activation of intestinal epithelial cell necrosis, should not be overlooked. Mechanistically, we identified a relationship between the expression of upstream factors, including Enterovirus D68 (EV-D68), Heterogeneous Nuclear Ribonucleoprotein D (HNRNPD or AUF1), Endoplasmic Reticulum Protein 57 (ERp57), and Progranulin (PGRN), and downstream factors such as Meiotic Recombination Protein Spo11 (Spo11), AMP-Activated Protein Kinase (AMPK), Double-Strand-Break Repair Protein Rad21 Homolog (Rad21L), IκB Kinase (IKK), and TDP-43. Conclusion: TDP-43 plays a pathological role in neurodegeneration, of which, the expression is related to phosphorylation, EV-d68, and HNRNPD.