The article reviews the interplay between neuroinflammation and the glymphatic system in the context of neurodegenerative disorders. Neurodegeneration, characterized by the progressive loss of neurons, is associated with protein aggregation, particularly β-amyloid (Aβ) in Alzheimer's disease (AD) and α-synuclein (α-Syn) in Parkinson's disease (PD). Neuroinflammation, involving microgliosis and astrogliosis, is a key component of neurodegenerative diseases, contributing to their progression. The glymphatic system, which facilitates the clearance of metabolic waste from the brain, plays a crucial role in maintaining brain homeostasis. Astrocytes, the most abundant glial cells in the brain, are essential for the glymphatic system's function and inflammatory responses. Aquaporin 4 (AQP4), a water channel protein expressed on astrocytic end-feet, is vital for the glymphatic flow and clearance of waste products. Disturbances in AQP4 polarization and expression can impair glymphatic function, leading to increased protein aggregation and neuroinflammation. Protein aggregates, such as Aβ and α-Syn, contribute to a vicious cycle of impaired glymphatic clearance and neuroinflammation, exacerbating neurodegeneration. Additionally, the gut-brain axis and microbiome may influence neuroinflammatory and neurodegenerative processes through their impact on the blood-brain barrier (BBB) and systemic inflammation. The article highlights the complex interplay between these factors and emphasizes the need for further research to understand and potentially target these processes for therapeutic intervention in neurodegenerative disorders.The article reviews the interplay between neuroinflammation and the glymphatic system in the context of neurodegenerative disorders. Neurodegeneration, characterized by the progressive loss of neurons, is associated with protein aggregation, particularly β-amyloid (Aβ) in Alzheimer's disease (AD) and α-synuclein (α-Syn) in Parkinson's disease (PD). Neuroinflammation, involving microgliosis and astrogliosis, is a key component of neurodegenerative diseases, contributing to their progression. The glymphatic system, which facilitates the clearance of metabolic waste from the brain, plays a crucial role in maintaining brain homeostasis. Astrocytes, the most abundant glial cells in the brain, are essential for the glymphatic system's function and inflammatory responses. Aquaporin 4 (AQP4), a water channel protein expressed on astrocytic end-feet, is vital for the glymphatic flow and clearance of waste products. Disturbances in AQP4 polarization and expression can impair glymphatic function, leading to increased protein aggregation and neuroinflammation. Protein aggregates, such as Aβ and α-Syn, contribute to a vicious cycle of impaired glymphatic clearance and neuroinflammation, exacerbating neurodegeneration. Additionally, the gut-brain axis and microbiome may influence neuroinflammatory and neurodegenerative processes through their impact on the blood-brain barrier (BBB) and systemic inflammation. The article highlights the complex interplay between these factors and emphasizes the need for further research to understand and potentially target these processes for therapeutic intervention in neurodegenerative disorders.