How does microglial INPP5D deficiency non-cell-autonomously induce neuronal TDP-43 pathology?

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Description

The abstract shows that microglial INPP5D deficiency promotes neuronal TDP-43 pathology in a non-cell-autonomous manner, but the intercellular signaling mechanisms are not explained. Understanding this pathway is critical since TDP-43 pathology occurs in multiple neurodegenerative diseases including AD-ALS comorbidity.

Gap type: unexplained_observation Source paper: Repression of RIPK1 kinase by INPP5D inhibits expression of diverse proinflammatory mediators and late-onset Alzheimer’s disease risk factors. (None, None, PMID:41633359)

Evidence summary

Resolved by hypothesis h-ccc05373: p38α Inhibitor and PRMT1 Activator Combination to Restore Physiological TDP-43 Phosphorylation-Methylation Balance. Score: 0.879. Supporting PMIDs: 39817908, NCT05869669, 39817908, NCT05869669, 39817908.

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