Ricerc@Sapienza

Microglia are the resident immune cells of the brain, crucial for the maintenance of the homeostasis in the CNS. When brain homeostasis is perturbed, microglia undergo a process of activation that profoundly change their morphology, to carry out specialized functions by releasing cytokines and chemokines. The morphological changes are driven by massive cytoskeletal modifications, that allow the cells to become from ramified to more ameboid. The role of the actin cytoskeleton in driving these morphological changes, and therefore the specialized functions of activated microglia, has been extensively studied, while the role of the tubulin cytoskeleton have been almost ignored. Microtubules represent a major scaffold in the cell for the transport of macromolecules, organelles, for maintaining the cell shape and for cell movement. Understanding the microtubule structure, organization and modifications that underlie the morphological changes of activated microglia can provide new tools to understand microglia activation process. Microglia activation is a salient feature of neuroinflammation, prominent in many neurodegenerative diseases. Recently, the centrosome - the main microtubule organizing center- dynamics has been correlated with the release of cytokines in activated macrophages. Thus, microtubule cytoskeleton modifications represent a crucial aspect of the morphological changes that are functional to drive specialized and diverse activated microglia functions, and targeting the microtubules can let to the disclosure of new mechanisms to modulate microglia-mediated neuroinflammation.
Here, we aim to describe for the first time the organization of microglia microtubule cytoskeleton, to identify microglia cytoskeletal mechanisms responsible for morphology changes in activated cells, and to target structural elements driving microglia release of inflammatory cytokines.