PHAGOCYTIC ROLE OF ASTROCYTES: UNVEILING MOLECULAR SIGNATURES AND CROSSTALK WITH MICROGLIA IN NEURODEGENERATIVE DISEASES

Neurodegenerative diseases (NDs) comprise a spectrum of heterogeneous disorders characterised by the structural and functional degeneration of the central and peripheral nervous systems (CNS, PNS), due to the presence of abnormal neuronal protein assemblies, that are packaged into insoluble inclusion bodies and released into the extracellular milieu via unconventional pathways.
CNS diseases have been often viewed from a neurocentric point of view, but more recently, glial cells have received considerable attention for their key role in removing unwanted and potentially harmful substances from the extracellular environment. The removal of misfolded protein aggregates from the extracellular milieu is crucial for limiting the pathophysiology of NDs and is primarly the responsibility of phagocytic cells, particularly microglia.
Recent studies have described astrocytes as phagocytic cells, demonstrating their involvement in the removal of protein aggregates, such as α-synuclein (α-syn), from the extracellular milieu, working in conjunction with microglia to maintain a clean microenvironment within the CNS.
The aim of this work is to elucidate the extent and importance of astrocyte involvement in the clearance of extracellular protein aggregates, with a particular focus on the metabolism of α-syn and its impact on astrocytes at the ultrastructural and functional level. Additionally, we examine the functional relationship between microglia and astrocytes, in order to determine how these two cell types interact with each other in the clearance of protein aggregates.