The Brain

Inflammatory and Age-Dependent Neurodegeneration

The adult Drosophila central nervous system (CNS) consists of ~200,000-300,000 cells , ~90% of which are neurons, with the remaining 10% being glia. The development of Drosophila CNS involves the production of many excess neurons, which must be removed to leave behind the precise set of neurons required by the adult animals. Excess neurons are removed through programmed cell death (PCD) and subsequent clearance by glia in a process known as phagocytosis, or cell eating. In Drosophila, glia use the phagocytosis receptor Draper to recognize and engulf cell corpses. In flies lacking the draper gene, neuronal cell corpses accumulate in development and persist in the brain until organism death. These flies also display age-dependent neurodegeneration. Guangmei and Yan aims to determine the mechanism through which this neurodegeneration occurs. In other organisms and tissues, persisting uncleared cell corpses lead to an overactive immune response. Overactive immunity in the brain is in turn associated with neurodegeneration, both in mammals and in Drosophila. Therefore, we are exploring the hypothesis that in draper mutants, persisting neuronal corpses induce an innate immune response in the brain, leading to neurodegeneration.