Apoptotic neurons and amyloid-beta clearance by phagocytosis in Alzheimer's disease: Pathological mechanisms and therapeutic outlooks

Neuronal survival and axonal renewal following central nervous system damage and in neurodegenerative illnesses, such as Alzheimer's disease (AD), can be enhanced by fast clearance of neuronal apoptotic debris, as well as the removal of amyloid beta (A beta) by phagocytic cells through the process of efferocytosis. This process quickly inhibits the release of proinflammatory and antigenic autoimmune constituents, enhancing the formation of a microenvironment vital for neuronal survival and axonal regeneration. Therefore, the detrimental features associated with microglial phagocytosis uncoupling, such as the accumulation of apoptotic cells, inflammation and phagoptosis, could exacerbate the pathology in brain disease. Some mechanisms of efferocytosis could be targeted by several promising agents, such as curcumin, URMC-099 and Y-P30, which have emerged as potential treatments for AD. This review aims to investigate and update the current research regarding the signaling molecules and pathways involved in efferocytosis and how these could be targeted as a potential therapy in AD.

Automated summary

Efficient clearance of neuronal apoptotic debris and Aβ through phagocytosis creates a microenvironment beneficial for neuronal survival and axonal regeneration, key in the treatment of AD. Disruption of microglial phagocytic function may exacerbate the pathology of brain diseases. Some promising drugs may target the mechanisms of phagocytosis to treat AD.