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At least in some individuals, the development of major depressive disorder (MDD) appears to be significantly influenced by neuroinflammation. Microglia, which are situated within the brain, represent a type of immune cell that exhibits the capability to transform into a reactive state in response to inflammatory attacks. This unique ability substantiates the critical role microglia play in the initial stages of neuroinflammation. Empirical studies have revealed that microglia are proficient in discerning infections or damaged cells, thereby instigating a cytotoxic response that exacerbates the damage inflicted on brain cells. However, microglia display a wide range of reactions to injury and may potentially contribute to the process of recuperation and the reinstatement of impaired tissues. It is possible that changing the phenotype of microglia through the regulation of inflammatory pathways is essential in order to harness neuroinflammation in MDD. This study examines potential new treatment paths for modulating neuroinflammation in brain disorders by analyzing canonical proinflammatory, anti-inflammatory, and metabolic mechanisms in microglia.  the primary focus is on the major depressive disorder (MDD), but will also discuss other brain diseases.