Neuroinflammation plays a critical role in neurodegenerative diseases such as Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis (ALS). Microglia and astrocytes are key regulators of the immune response in the central nervous system (CNS). These cells can adopt either neurotoxic (M1/M2) or neuroprotective (M2/A2) phenotypes, but their roles are complex and context-dependent. The activation of microglia and astrocytes is influenced by disease progression, regional location, and environmental factors. Understanding their roles is essential for developing effective therapies. Microglia are the primary innate immune cells in the CNS, responsible for detecting pathogens and maintaining homeostasis. They can be activated by various stimuli, leading to the release of pro-inflammatory cytokines that may contribute to neurodegeneration. However, microglia can also have neuroprotective functions, such as clearing pathological agents and promoting tissue repair. Astrocytes, the most abundant glial cells, regulate blood flow, maintain the blood-brain barrier, and support neuronal function. They can also become activated in response to inflammation, contributing to both neuroinflammation and neuroprotection. In neurodegenerative diseases, the balance between pro-inflammatory and neuroprotective glial responses is crucial. Dysfunctional microglia and astrocytes can exacerbate disease progression by releasing harmful inflammatory mediators. Conversely, neuroprotective glial activation can help mitigate neurodegeneration. Biomarkers such as sTREM2 and imaging techniques like PET can help assess microglial activation and guide therapeutic interventions. Therapeutic strategies targeting neuroinflammation include anti-inflammatory drugs, modulators of microglial activation, and agents that promote neuroprotective glial functions. However, clinical trials have shown mixed results, highlighting the complexity of glial cell phenotypes and the need for targeted approaches. Future research should focus on understanding the dynamic interactions between microglia and astrocytes, identifying effective biomarkers, and developing therapies that modulate glial responses to improve outcomes in neurodegenerative diseases.Neuroinflammation plays a critical role in neurodegenerative diseases such as Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis (ALS). Microglia and astrocytes are key regulators of the immune response in the central nervous system (CNS). These cells can adopt either neurotoxic (M1/M2) or neuroprotective (M2/A2) phenotypes, but their roles are complex and context-dependent. The activation of microglia and astrocytes is influenced by disease progression, regional location, and environmental factors. Understanding their roles is essential for developing effective therapies. Microglia are the primary innate immune cells in the CNS, responsible for detecting pathogens and maintaining homeostasis. They can be activated by various stimuli, leading to the release of pro-inflammatory cytokines that may contribute to neurodegeneration. However, microglia can also have neuroprotective functions, such as clearing pathological agents and promoting tissue repair. Astrocytes, the most abundant glial cells, regulate blood flow, maintain the blood-brain barrier, and support neuronal function. They can also become activated in response to inflammation, contributing to both neuroinflammation and neuroprotection. In neurodegenerative diseases, the balance between pro-inflammatory and neuroprotective glial responses is crucial. Dysfunctional microglia and astrocytes can exacerbate disease progression by releasing harmful inflammatory mediators. Conversely, neuroprotective glial activation can help mitigate neurodegeneration. Biomarkers such as sTREM2 and imaging techniques like PET can help assess microglial activation and guide therapeutic interventions. Therapeutic strategies targeting neuroinflammation include anti-inflammatory drugs, modulators of microglial activation, and agents that promote neuroprotective glial functions. However, clinical trials have shown mixed results, highlighting the complexity of glial cell phenotypes and the need for targeted approaches. Future research should focus on understanding the dynamic interactions between microglia and astrocytes, identifying effective biomarkers, and developing therapies that modulate glial responses to improve outcomes in neurodegenerative diseases.