TDP43

 

https://www.sciencedaily.com/releases/2026/03/260314030507.htm

 

TAR DNA-binding protein 43 (TDP-43) is a crucial RNA/DNA-binding protein that normally regulates RNA splicing, stability, and transport within the cell nucleus. Pathological TDP-43 mislocalizes to the cytoplasm, forming insoluble aggregates (proteinopathy) that drive neurodegeneration in ALS, 50% of FTD cases, and some Alzheimer’s cases, resulting in both loss of nuclear function and gain of toxicity. 

 

Key Aspects of TDP-43:

Full Name/Function: Transactive Response DNA Binding Protein 43 kDa (TDP-43). It acts as a nuclear scaffold for DNA repair and manages RNA metabolism.

Pathology: In neurodegenerative diseases, TDP-43 leaves the nucleus, accumulates in the cytoplasm, and forms neurotoxic aggregates.

Associated Diseases: Cardinal protein in Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD). Also found in LATE, Alzheimer’s disease, and Chronic Traumatic Encephalopathy (CTE).

Mutations: Mutations in the TARDBP gene, which encodes TDP-43, are associated with familial ALS/FTD, though protein aggregation can occur in sporadic cases without mutations.

Mechanism: Pathological TDP-43 is characterized by phosphorylation, ubiquitination, and truncated forms, leading to mitochondrial stress and reduced cell survival. 

 

Images of TDP-43 pathology typically show immunohistochemistry (IHC) staining, with normal cells showing brown nuclear staining, while pathological cells show brown aggregate deposits in the cytoplasm. 

-googAI

 

https://m.youtube.com/watch?v=lTSltDmVtLM&t=36s&pp=2AEkkAIB

 

 

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