NADPH Oxidase Inhibition Promotes Brain Resilience by Attenuating Tauopathy and Neuroinflammation in Alzheimer's Disease.

ABSTRACT: Alzheimer's disease (AD) associates closely associated with the activation of NADPH oxidase (Nox) isozymes. CRB-2131, a novel oxadiazole derivative, is identified as a potently suppresses Nox isozymes. It inhibits reactive oxygen species production (ROS) by hippocampal neuronal and microglial cells and reduces microglial activation. Prophylactic (starting at 3.5 months of age) and therapeutic (starting at 6 months of age) oral administration with CRB-2131 for 10 weeks in 5XFAD mice reduced hippocampal superoxide levels, lipid peroxidation, Tau phosphorylation, and neuroinflammation. Prophylactic and therapeutic CRB-2131 treatment of 5XFAD mice restored their impaired cognition as shown by the novel-object recognition, Y-maze, and Morris water-maze tests. CRB-2131 treatment increased mature

SUBMITTER: Lee J 

PROVIDER: S-EPMC12622451 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature