Researchers reveal metabolic and inflammatory roles of glial cells

Neurons have been the main focus in studying Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, ischemic stroke, and hypoxic-ischemic brain injury. However, increasing evidence suggests that the progression of these disorders is influenced not only by neuronal damage itself but also by the behavior of glial cells, especially microglia and astrocytes.

A study published in Ageing Research Reviews, led by MA Yinzhong's team from the Shenzhen Institutes of Advanced Technology (SIAT) of the Chinese Academy of Sciences, offers a comprehensive view of how glial cells contribute to disease progression through metabolic reprogramming, inflammatory amplification, and neurovascular dysfunction.

Researchers demonstrated that under normal conditions, microglia and astrocytes are crucial for maintaining homeostasis in the central nervous system. Microglia constantly monitor the brain environment and participate in immune regulation and debris removal, while astrocytes are involved in neurotransmitter recycling, lipid transport, metabolic support, and blood-brain barrier maintenance.

In disease states, however, the researchers showed that both cell types experienced significant functional changes. Microglia shifted from homeostatic surveillance to inflammatory or repair-related states, while astrocytes adopted reactive phenotypes that could be either neuroprotective or neurotoxic.

Furthermore, the researchers found that glial dysfunction is closely connected to metabolism. Activated microglia often switch from oxidative phosphorylation to glycolysis, which encourages cytokine release and the production of reactive oxygen species. Conversely, astrocytes frequently show disrupted lipid metabolism, impaired cholesterol transport, and lipid droplet buildup, all of which can weaken neuronal support and worsen inflammation.

Furthermore, researchers identified the pathological feedback loops between microglia and astrocytes. Once activated, these cells reinforce each other through inflammatory mediators, complement signaling, metabolites, and extracellular vesicles, creating a self-sustaining cycle of chronic neuroinflammation. This process extends beyond neurons and involves the blood-brain barrier and the neurovascular unit, helping to explain why many neurodegenerative and cerebrovascular diseases share common patterns of injury progression.

This study suggests that glial cells should be seen not just as inflammatory responders but as key regulators linking metabolism, immunity, and neurovascular stability. It opens new avenues for therapeutic approaches that reprogram glial states and restore brain homeostasis.