What molecular mechanisms cause acetylated tau to specifically inhibit chaperone-mediated autophagy?

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Priority

82%

Importance

85%

Tractability

80%

Market price

50%

Description

The study shows acetylated tau inhibits CMA and gets rerouted to other degradation pathways, but the specific molecular interactions responsible for this inhibition are not explained. Understanding this mechanism is crucial for developing targeted therapeutic interventions to restore CMA function in tauopathies.

Gap type: unexplained_observation Source paper: Acetylated tau inhibits chaperone-mediated autophagy and promotes tau pathology propagation in mice. (2021, Nature communications, PMID:33854069)

Evidence summary

Resolved by hypothesis h-51e7234f: APOE-Dependent Autophagy Restoration. Score: 0.877. Supporting PMIDs: 31578018, 34031601, 33692541, 31235664, 29566236.

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