ROCK inhibitor Ripasudil reduces Alzheimer pathological proteins and enhances cellular bioenergetics

In AppNL-G-F knock-in mice, ripasudil (30 mg/kg) significantly reduces Tau and pTau 396 after 3 hours, alongside rapid brain penetration.

• Why it matters: Alzheimer pathology is linked to tau abnormalities, and ROCK inhibitors are being explored to modulate these disease proteins and related cellular functions.
• What they did: Mice received ripasudil, brain proteomes were profiled by Tandem Mass Tag labeling versus saline, and AD-patient-derived NSCs were tested with a Seahorse Mito Stress Test after treatment.
• The result: In NSCs, ripasudil significantly increases basal oxygen consumption, ATP-linked respiration, maximal respiration, and reserve capacity, implying improved mitochondrial bioenergetics while tau and pTau 396 decrease in mouse brains.

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