Therapeutic targeting of immunometabolism in Alzheimer's disease reveals a critical reliance on Hexokinase 2 dosage on microglial activation and disease progression.

ABSTRACT: Microgliosis and neuroinflammation are prominent features of Alzheimer's disease (AD). Disease-responsive microglia meet their increased energy demand by reprogramming metabolism, specifically, switching to favor glycolysis over oxidative phosphorylation. Thus, targeting of microglial immunometabolism might be of therapeutic benefit for treating AD, providing novel and often well understood immune pathways and their newly recognized actions in AD. We report that in the brains of 5xFAD mice and postmortem brains of AD patients, we found a significant increase in the levels of Hexokinase 2 (HK2), an enzyme that supports inflammatory responses by rapidly increasing glycolysis. Moreover, binding of HK2 to mitochondria has been reported to regulate inflammation by preventing mitochondrial dysfu

SUBMITTER: Codocedo JF 

PROVIDER: S-EPMC10680613 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature