The activation of microglia by the complement system in neurodegenerative diseases

Neurodegenerative diseases (NDDs) are a group of neurological disorders characterized by the progressive loss of neuronal structure and function, leading to cognitive and behavioral impairments. Despite significant research advancements, there is currently no definitive cure for NDDs. With global aging on the rise, the burden of these diseases is becoming increasingly severe, highlighting the urgency of understanding their pathogenesis and developing effective therapeutic strategies. Microglia, specialized macrophages in the central nervous system, play a dual role in maintaining neural homeostasis. They are involved in clearing cellular debris and apoptotic cells, but in their activated state, they release inflammatory factors that contribute significantly to neuroinflammation. The complement system (CS), a critical component of the innate immune system, assists in clearing damaged cells and proteins. However, excessive or uncontrolled activation of the CS can lead to chronic neuroinflammation, exacerbating neuronal damage. This review aims to explore the roles of microglia and the CS in the progression of NDDs, with a specific focus on the mechanisms through which the CS activates microglia by modulating mitochondrial function. Understanding these interactions may provide insights into potential therapeutic targets for mitigating neuroinflammation and slowing neurodegeneration.