Why does p62 persist after stress granule and TDP-43 aggregate clearance during recovery?

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Description

The authors observe that while stress granules and TDP-43 aggregates resolve within 72 hours of stress removal, the autophagy marker p62 remains elevated. This suggests autophagy dysfunction may be both cause and consequence of TDP-43 pathology, but the mechanistic relationship is unresolved.

Gap type: unexplained_observation Source paper: Chronic stress induces formation of stress granules and pathological TDP-43 aggregates in human ALS fibroblasts and iPSC-motoneurons. (2020, Neurobiology of disease, PMID:32827688)

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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