Therapeutic approaches to microglial dysfunction in Alzheimer's disease: Enhancing phagocytosis and metabolic regulation

Microglia are essential in neurogenesis, synaptic pruning, and homeostasis. Nevertheless, aging, and cellular senescence may modify their role, causing them to shift from being shields to being players of neurodegeneration. In the aging brain, the population of microglia increases, followed by enhanced activity of genes related to neuroinflammation. This change increases their ability to cause inflammation, resulting in a long-lasting state of inflammation in the brain that harms the condition of neurons. In Alzheimer's Disease (AD), microglia are located inside amyloid plaques and exhibit an inflammatory phenotype characterized by a diminished ability to engulf and remove waste material, worsening the illness's advancement. Genetic polymorphisms in TREM2, APOE, and CD33 highlight the significant impact of microglial dysfunction in AD. This review examines therapeutic approaches that aim to address microglial dysfunction, such as enhancing the microglial capability to engulf and remove amyloid-β clumps and regulating microglial metabolism and mitochondrial activity. Microglial transplanting and reprogramming advancements show the potential to restore their ability to reduce inflammation. Although there has been notable advancement, there are still voids in our knowledge of microglial biology, including their relationships with other brain cells. Further studies should prioritize the improvement of human AD models, establish standardized methods for characterizing microglia, and explore how various factors influence microglial responses. It is essential to tackle these problems to create effective treatment plans that focus on reducing inflammation in the brain and protecting against damage in age-related neurodegenerative illnesses.