Microglia are innate immune cells resident in the brain, analogous to macrophages elsewhere in the body, but with a portfolio of duties that also includes assisting in the maintenance and function of neural networks. With age, microglia become more inflammatory and active, and this contributes to the onset and progression of neurodegenerative conditions. There are many known contributing causes, one of which is the mitochondrial dysfunction that occurs in cells throughout the body.
The best way to determine just how much of the problem of inflammatory microglia is downstream of mitochondrial dysfunction is to fix that dysfunction, but the presently available approaches that improve mitochondrial function in aged tissues (vitamin B3 derivatives, mitoQ, urolithin A, and so forth) are not powerful enough to make a sizable difference. It may be that mitochondrial transplantation therapies will be needed in order to robustly determine whether fixing mitochondria can slow or reverse neurodegenerative conditions to a useful degree.
Microglia, the primary immune cells of the central nervous system, play a pivotal role in maintaining brain homeostasis. Recent studies have highlighted the involvement of microglial dysfunction in the pathogenesis of various age-related neurodegenerative diseases, such as Alzheimer's disease. Moreover, the metabolic state of microglia has emerged as a key factor in these diseases.
Interestingly, aging and neurodegenerative diseases are associated with impaired mitochondrial function and a metabolic shift from oxidative phosphorylation to glycolysis in microglia. This metabolic shift may contribute to sustained microglial activation and neuroinflammation. Furthermore, the leakage of mitochondrial DNA into the cytoplasm, because of mitochondrial dysfunction, has been implicated in triggering inflammatory responses and disrupting brain function.
This review summarizes recent advances in understanding the role of microglial metabolic shifts, particularly glycolysis, and mitochondrial dysfunction. It also explores the potential of targeting microglial metabolism, for instance by modulating mitophagy or intervening in specific metabolic pathways, as a novel therapeutic approach for changes in brain function and neurodegenerative diseases associated with aging.
Link: https://doi.org/10.3164/jcbn.24-202
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