Roles of microglia in CNS
Microglia are the sentinel immune cells of the CNS and play a critical role in maintaining CNS health, or homeostasis, and responding to damage caused by disease
They continuously sense and respond to multiple types of signals, including those generated by infection, or by normal cell death and myelin turnover. Microglia coordinate multiple signal-specific downstream responses, such as potentiation of microglial survival and proliferation, activation of microglial phagocytosis, pruning of excess neural connections to maintain synaptic health, stimulation of lysosomal function, and maintenance of lipid and cholesterol metabolism.
Our initial focus on microglia and microglia-targeted therapeutics is based on discoveries linking microglia to both rare, often inherited, and common neurodegenerative diseases that either result from or are associated with genetic mutations or variations. These conditions include leukoencephalopathies and leukodystrophies, a set of rare, mainly inherited disorders affecting neurons and white matter. Specific examples of these microglia-associated genetic disorders include adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), cerebral adrenoleukodystrophy (cALD), Krabbe, metachromatic leukodystrophy (MLD), as well as genetic subpopulations of Alzheimer’s disease (AD) carrying genetic variants affecting microglial function.
