Role of Triggers on the Structural and Functional Facets of TAR DNA-binding Protein 43

TAR DNA-binding protein 43 (TDP-43) mitigates cellular function, but the dynamic nucleus -cytoplasm shuttling of TDP-43 is disrupted in diseases, such as Amyotrophic Lateral Sclerosis (ALS). The poly-morphic nature of the TDP-43 structures in vitro and in vivo is a result of environmental factors leading to the pro-tein pathogenesis. Once the triggers which mitigate TDP-43 biochemistry are identified, new therapies can be developed. This review aims to illustrate recent discoveries in the diversity of TDP-43 structures (amyloidogenic and non-amyloidogenic) and highlight the triggers which result in their formation.(c) 2022 IBRO. Published by Elsevier Ltd. All rights reserved.

Automated summary

TDP-43 plays a role in cellular function, but its nucleus-cytoplasm shuttling is disrupted in diseases like ALS. The variability of TDP-43 structures is influenced by environmental factors that contribute to protein pathogenesis. Identifying triggers that affect TDP-43 biochemistry could lead to new therapies. This review discusses recent findings on the diversity of TDP-43 structures and the triggers that lead to their formation.