Gliotoxicity and Glioprotection: the Dual Role of Glial Cells

Quincozes-Santos, André; Santos, Camila Leite; de Souza Almeida, Rômulo Rodrigo; da Silva, Amanda; Thomaz, Natalie K.; Costa, Naithan Ludian Fernandes; Weber, Fernanda Becker; Schmitz, Izaviany; Medeiros, Lara Scopel; Medeiros, Lívia; Dotto, Bethina Segabinazzi; Dias, Filipe Renato Pereira; Sovrani, Vanessa; Bobermin, Larissa Daniele

Glial cells (astrocytes, oligodendrocytes and microglia) are critical for the central nervous system (CNS) in both physiological and pathological conditions. With this in mind, several studies have indicated that glial cells play key roles in the development and progression of CNS diseases. In this sense, gliotoxicity can be referred as the cellular, molecular, and neurochemical changes that can mediate toxic effects or ultimately lead to impairment of the ability of glial cells to protect neurons and/or other glial cells. On the other hand, glioprotection is associated with specific responses of glial cells, by which they can protect themselves as well as neurons, resulting in an overall improvement of the CNS functioning. In addition, gliotoxic events, including metabolic stresses, inflammation, excitotoxicity, and oxidative stress, as well as their related mechanisms, are strongly associated with the pathogenesis of neurological, psychiatric and infectious diseases. However, glioprotective molecules can prevent or improve these glial dysfunctions, representing glial cells-targeting therapies. Therefore, this review will provide a brief summary of types and functions of glial cells and point out cellular and molecular mechanisms associated with gliotoxicity and glioprotection, potential glioprotective molecules and their mechanisms, as well as gliotherapy. In summary, we expect to address the relevance of gliotoxicity and glioprotection in the CNS homeostasis and diseases.