Playing with phagocytic glia to affect neurodegeneration

In vertebrates and invertebrates, phagocytic glia remove unwanted and potentially dangerous material in the developing and mature central nervous system (CNS). During development, glial phagocytosis of apoptotic neurons is crucial for establishing a functional CNS. In the adult brain, phagocytic glia protect neurons from harmful effects of infectious agents, injured cells and protein aggregates associated with neurodegeneration. However, uncontrolled glial phagocytosis may result in irreversible damage making regulation of glial phagocytic ability extremely important for the wellbeing of the nervous system. Whereas some studies revealed that glial phagocytosis protects the adult brain from neurodegeneration, we and others showed that over-activity of phagocytic glia can also be deleterious due to phosphatidylserine-mediated phagocytosis of live neurons (phagoptosis). We demonstrated that elevated expression of the phagocytic receptors SIMU and Drpr in adult Drosophila glia leads to a loss of both dopaminergic and GABAergic neurons, accompanied by motor dysfunction and shortened lifespan. This neuronal loss was not linked to neuronal apoptosis but rather to phosphatidylserine-mediated phagoptosis of live neurons by hyper-phagocytic glia. Based on these findings, we started to explore whether prevention of phagoptosis may affect neurodegeneration in adult fly brain. Using Drosophila model for Parkinson`s disease we found that masking phosphatidylserine exposed on stressed but viable neurons significantly improved flies motor activity and prolonged their lifespan. Moreover, compared to the Parkinson`s disease model flies, masking phosphatidylserine increased the number of dopaminergic neurons suggesting that this treatment rescued stressed neurons and might help fighting neurodegeneration.