The review discusses the roles of the glymphatic system and neuroinflammation as key factors in neurodegeneration. The glymphatic system, which clears metabolic waste from the brain, is impaired in neurodegenerative diseases like Alzheimer's and Parkinson's. Neuroinflammation, involving microglia and astrocytes, also contributes to disease progression. Astrocytes are essential for glymphatic function and inflammatory responses. AQP4, a water channel in astrocytes, is crucial for glymphatic clearance and influences inflammatory processes. Protein aggregates, such as amyloid-beta and alpha-synuclein, are linked to both glymphatic dysfunction and neuroinflammation. The gut-brain axis and microbiome may also impact these processes. Dysbiosis, or microbial imbalance, is associated with neuroinflammation and may affect the glymphatic system. The interplay between these factors creates a vicious cycle that drives neurodegeneration. The review highlights the importance of understanding these mechanisms to develop effective therapies for neurodegenerative disorders.The review discusses the roles of the glymphatic system and neuroinflammation as key factors in neurodegeneration. The glymphatic system, which clears metabolic waste from the brain, is impaired in neurodegenerative diseases like Alzheimer's and Parkinson's. Neuroinflammation, involving microglia and astrocytes, also contributes to disease progression. Astrocytes are essential for glymphatic function and inflammatory responses. AQP4, a water channel in astrocytes, is crucial for glymphatic clearance and influences inflammatory processes. Protein aggregates, such as amyloid-beta and alpha-synuclein, are linked to both glymphatic dysfunction and neuroinflammation. The gut-brain axis and microbiome may also impact these processes. Dysbiosis, or microbial imbalance, is associated with neuroinflammation and may affect the glymphatic system. The interplay between these factors creates a vicious cycle that drives neurodegeneration. The review highlights the importance of understanding these mechanisms to develop effective therapies for neurodegenerative disorders.