Pharmacological modulation of CSF1R activation to control microglial proliferation in neurodegenerative disease

Microglia are the main resident immune cells in the central nervous system. The expansion and activation of microglia is a hallmark of many neurodegenerative diseases including Alzheimer’s disease or prion disease. Colony-stimulating factor 1 receptor (CSF1R) is involved in the control of the microglial proliferation and can be activated by two independent ligands, CSF1 and IL-34. These two ligands display differences in the signalling cascade suggesting a complementary role. However, although CSF1 and IL-34 are expressed in many organs, IL-34 appears particularly expressed in the developing and adult brain, suggesting that maintenance of the populations of microglia is dependent on IL-34-CSF1R signaling. The aim of this project is the evaluation of novel strategies that can be used to modulate microglia proliferation in neurodegenerative diseases by using an in vivo model of neurodegeneration (prion disease; ME7).