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

•TDP-43 aggregation is highly dependent on the protein domains.•Aggregation and morphological outcomes are influenced by triggers.•Polymorphism of TDP-43 is a promising drug target. Nuclear TAR DNA-binding protein 43 (TDP-43) mitigates cellular function, but the dynamic nucleus-cytoplasm shuttling o...

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Bibliographic Details
Published in:Neuroscience 2023-02, Vol.511, p.110-130
Main Authors: Camilus, Nayomi, Quintero Arias, Carlos, Martic, Sanela
Format: Article
Language:English
Subjects:
ALS
amyloids
Amyotrophic Lateral Sclerosis - metabolism
Cell Nucleus - metabolism
Cytoplasm - metabolism
DNA-Binding Proteins - metabolism
Humans
morphologies
neurodegeneration
protein aggregation
TDP-43
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Summary:•TDP-43 aggregation is highly dependent on the protein domains.•Aggregation and morphological outcomes are influenced by triggers.•Polymorphism of TDP-43 is a promising drug target. Nuclear 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 polymorphic nature of the TDP-43 structures in vitro and in vivo is a result of environmental factors leading to the protein 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.
ISSN:0306-4522
1873-7544
DOI:10.1016/j.neuroscience.2022.11.027