TDP-43 Acetylation at the Neuroimmune Interface: A Hypothesis-Driven Framework for Peripheral Inflammatory Stratotypes in ALS - PubMed
3 hours ago
- #ALS immunopathology
- #TDP-43 acetylation
- #neuroimmune interface
- TDP-43 acetylation may link motor neuron degeneration to systemic immune responses in ALS, acting as a neuroimmune interface.
- Acetylation affects TDP-43's conformation, trafficking, and immunogenicity when it mislocalizes to the periphery.
- The review uses data from single-cell transcriptomics, proteomics, and clinical phenotyping to associate acetylated TDP-43 with peripheral inflammatory signatures in ALS.
- Two provisional endotypes are proposed, involving monocyte reprogramming, cytokine modules, and BBB dysfunction, as clinically actionable pathways.
- TDP-43 acetylation could be a therapeutic target via p300/CBP-HDAC or sirtuin pathways, shifting ALS treatment toward stratified immunotherapy based on peripheral signatures.