ROCK inhibitor Ripasudil reduces Alzheimer pathological proteins and enhances cellular bioenergetics

Rho-associated kinase (ROCK) inhibitors, like ripasudil, have shown promise as potential treatments for Alzheimer's disease (AD). In this study, the researchers sought to assess the effectiveness of ripasudil on AD-related pathological proteins in mice. After administering ripasudil to AppNL-G-F knock-in mice at a dose of 30 mg/kg, the investigators analyzed the proteomic profiles of the treated mice's brains and compared them to those of untreated mice.

Additionally, they treated human neural stem cells derived from AD patients with ripasudil and evaluated the impact on mitochondrial activity using a Seahorse Mito Stress Test.

The study's results indicated that ripasudil rapidly reached maximum concentration in the mouse brains within half an hour of injection. Bioinformatics analysis of the proteomic profiles revealed alterations in the expression of chromosome components. Furthermore, the Mito Stress Test of the AD-patient-derived neural stem cells treated with ripasudil demonstrated significant improvements in basal oxygen consumption, ATP-linked respiration, maximal respiration, and reserve capacity oxygen consumption compared to untreated cells.

Crucially, the researchers observed a significant reduction in tau and phosphorylated tau 396 in the brains of mice treated with ripasudil.

These findings suggest that ripasudil may serve as a feasible and promising therapeutic agent for AD, given its ability to reduce pathological tau protein levels and enhance cellular bioenergetics.