Interrelation of Oxidative Stress and Inflammation in Neurodegenerative Disease: Role of TNF

Figure 4

Interrelation of ROS and inflammatory cytokines in neurodegeneration. An initial neuronal damage can promote inflammation by activating the canonical NFκB pathway in glia cells via TLR activation resulting in the expression of proinflammatory cytokines and generation of ROS/RNS. Proinflammatory cytokines, in particular TNF, can promote neurodegeneration by further activating NFκB in glia cells, but also by damaging mitochondria in neurons resulting in increased ROS formation or by directly inducing neuronal cell death. ROS can further activate NFκB signaling in glia cells thereby promoting a sustained proinflammatory response. In addition, excess ROS/RNS formation by mitochondrial damage or by activated microglia and astrocytes can exacerbate neurodegeneration by damaging DNA, proteins, and membranes. Moreover, altered neuronal proteins, such as Aβ and α-synuclein, can promote ROS formation, for example, by impairing mitochondrial function. This interrelation of ROS promoting inflammation and TNF promoting ROS production can, when uncontrolled, ultimately result in chronic neurodegeneration.