Neuroinflammation and Glial Phenotypic Changes in Alpha-Synucleinopathies

The role of neuroinflammation has been increasingly recognized in the field of neurodegenerative diseases. Many studies focusing on the glial cells involved in the inflammatory responses of the brain, namely microglia and astroglia, have over the years pointed out the dynamic and changing behavior of these cells, accompanied by different morphologies and activation forms. This is particularly evident in diseased conditions, where glia react to any shift from homeostasis, acquiring different phenotypes. Particularly for microglia, it has soon become clear that such phenotypes are multiple, as multiple are the functions related to them. Several approaches have over time revealed different facets of microglial phenotypic diversity, and advanced genetic analyses, in recent years, have added new insights into microglial heterogeneity, opening novel scenarios that researchers have just started to explore. Among neurodegenerative diseases, an important section is represented by alpha-synucleinopathies. Here alpha-synuclein accumulates abnormally in the brain and, depending on its pattern of distribution, leads to the development of different clinical conditions. Also for these proteinopathies, neuroinflammation and glial activation have been identified as constant and crucial factors during disease development. In the present review we will address the current literature about glial phenotypic changes with respect to alpha-synucleinopathies, as well as consider the pathophysiological and therapeutic implications of such a dynamic cellular behavior.