**Acknowledgements**

The failure in these processes produces oxidation of proteins; lipids and DNA; consequently, organelle dysfunction; and after that neuronal damage. The critical organelle affected is the mitochondria, whose disruption induces reduction in ATP generation and apoptosis or necrosis [51]. As previously described the viral infection induced an increase in ROS production directly in CNS cells or indirectly by the infiltrated activated immune system cells, which use

**Figure 3.** The imbalance of pro-oxidants induces oxidative stress and cell damage. The vulnerability of the CNS: ↓GSH

 consumption. Inflammation triggers microglia. Activated microglia releases inflammatory cytokines, ROS, and RNS. Microglia and astrocytes can be activated via pattern recognition receptors. During astrocyte activation, these cells released ROS, RNS, and chemokines. In this microenvironment neurons presented macromolecule oxidation,

Glial cells (astrocytes and microglia) play important roles in maintaining CNS homeostasis through some processes, including reduction of oxidative stress. During neurodegenerative disorder glial cells release some factors to reestablish integrity and repair damaged cells. However, during the chronic inflammation, the glial activation causes an increase of ROS production and other neurotoxic mediators, leading a neuronal damage [52]. The principal cell type involved in CNS inflammation is the microglia. Microglia expresses some pattern recognition receptors that are engaged by pathogen-associated molecular patterns, triggering microglia activation. Activated microglia produced inflammatory mediators, such as prostaglandin

O2

dopaminergic neurons release matrix metalloproteinase 3, α-synuclein, and neuromelanin that superactivated microglia, inducing reactive microgliosis, enhancing of the neurotoxicity-related mediators, such ROS (**Figure 3**). Moreover, ROS exerts an important effect on microglia as the

, superoxide—O<sup>2</sup>

peroxynitrite). This phenomenon induces neuron damage. Damaged

•−), and reactive species nitrog-

ROS release as mechanism to control the infection (**Figure 3**).

, interleukin-1β TNFα, ROS (peroxide—H<sup>2</sup>

mitochondrial disruption, and, consequently, cell death.

E2

and ↑O2

74 Glutathione in Health and Disease

enous (RNS: NO; NOO\_

This work was supported by grants from Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ) and Oncobiologia Program. The author thanks Renata Novaes and Raquel C. de Albuquerque to collaborate in GSH-related works.
