Mitochondrial Quality Control in Microglia in the Aging Brain

Microglia are innate immune cells of the central nervous system, similar to macrophages elsewhere in the body. These cells become more inflammatory and dysfunctional with age, and this is implicated in the onset and progression of neurodegenerative conditions. Chronic inflammation is disruptive of tissue function, and in the brain is connected with a range of pathological mechanisms. Here, researchers discuss the loss of autophagy and related mitochondrial quality control characteristic of age, and how this might affect microglia. Inflammation and mitochondrial dysfunction are connected, one of the many ways in which age-related decline can provoke chronic, unresolved inflammation in tissues throughout the body.

Microglia, characterized by responding to damage, regulating the secretion of soluble inflammatory mediators, and engulfing specific segments in the central nervous system (CNS), function as key immune cells in the CNS. Emerging evidence suggests that microglia coordinate the inflammatory responses in CNS system and play a pivotal role in the pathogenesis of age-related neurodegenerative diseases (NDDs). Remarkably, microglia autophagy participates in the regulation of subcellular substances, which includes the degradation of misfolded proteins and other harmful constituents produced by neurons. Therefore, microglia autophagy regulates neuronal homeostasis maintenance and process of neuroinflammation.

Here, we provide an overview of the relationship between microglia autophagy and NDDs. The onset and progression of NDDs are associated with the accumulation of abnormal substances in the nervous system. Recent studies revealed that microglia autophagy removes harmful substances and abnormal aggregates produced by neurons in the nervous system and acts as a neuroprotective agent, which can help treat NDDs or control their progression. Meantime, manipulation of microglia autophagy also interrupts neuroinflammation in NDDs, maintain a state of equilibrium, and prevent disease progression. Therefore, the balance between microglia autophagy and neuroinflammation is of critical importance in NDDs.

Noticeably, potential drugs such as kaempferol, melatonin, and spermidine have been shown to balance microglia autophagy and neuroinflammation in NDDs. However, the mechanisms of interaction between microglia autophagy and neurons have not been sufficiently elucidated, such as how microglia autophagy remove toxic substances produced by neurons or glial cells or how microglia autophagy counteract abnormal neuronal death. More in-depth studies remain to be completed in this area.