Exploring and manipulating function of microglia in brain pathologies
Microglia are multifunctional immune cells of the brain executing various functions and rapidly responding to pathological insults. Brain injury, hypoxia, infection or aberrant protein accumulation may lead to chronic infl ammation with a progressive shift in microglia function towards infl ammatory phenotype and accumulation of immune cells. Under pathological conditions, the interplay of extrinsic signals directs microglia towards neuroprotective or detrimental phenotype. Molecular mechanisms of initiation, progression and termination of microglia-initiated infl ammatory responses in the brain, in particular gene networks and signaling pathways are poorly understood. Characterization of the global transcriptome of microglia exposed to infl ammatory or cytoprotective signals and analysis of signalling pathways revealed differences in expression of genes encoding cytokines/ chemokines and transcription regulators. Identifi cation of signalling pathways contributing to discrete microglia phenotypes and discovery of transcription regulators which may serve as “master switches” for induction of an infl ammatory phenotype, will allow to target specifi c functions of microglia. Therapeutic approaches targeting signal transduction in microglia will be discussed. A greater understanding of microglia functions coupled with advances in pharmacology and gene therapy will support development of functionally “engineered” microglia able to convey neuroprotection.