Abnormal Pathological Mechanisms of TDP-43 Protein and its Associated Pathway in Association with ALS

Abstract

TAR DNA binding protein 43 (TDP-43) is a nuclear protein with multiple RNA/DNA binding and editing functions. It is a key protein that causes Amyotrophic lateral sclerosis (ALS), frontotemporal lobe degeneration (FTLD), and other neurodegenerative diseases (NDDs). It is present in the patient’s tissue in the form of abnormal amyloid deposits and has been identified as the cause of the disease. The mutation site of TDP-43 is known to be associated with possible abnormal folding, and it has been determined that the cause of its formation of precipitation is the disruption of the phase separation state. The TDP-43 protein itself is well studied, but its interaction with other genes to cause ALS is relatively scarce. In this paper, the interaction of TDP-43 protein with HSPB1 and UNC13A will be introduced, which indirectly leads to the increased risk of ALS. And whether the association triggered by CE of UNC13A can specifically select and detect TDP-43 lesions at the early stage of the disease. By summarizing part of the pathogenic mechanism of TDP-43, this paper provides a reference for future further studies.