Ganoderma lucidum Protects Dopaminergic Neuron Degeneration through Inhibition of Microglial Activation

Figure 9

The molecular mechanisms between microglial activation and neuron death. Microglia can be activated by inflammatory trigger, such as LPS and other toxins and consequently produce proinflammatory factors and cytokines which on one side can cause auto-implication of ROS, NO and superoxide radicals to form highly oxidizing peroxynitrite species and also activate other resting microglia. TNF-dependent microglia activation in the SN creates an environment of oxidative stress through activation of NADPH oxidase. IL-1β can disrupt the blood brain barrier and facilitate the infiltration of leukocytes into CNS. All these factors can activate NF-κB, which can up-regulate pro-apoptotic genes leading to neuronal death. These events form a vicious circle leading to progressive neuronal degeneration. GL can inhibit the generation of microglia-derived toxic factors through its anti-inflammatory effect.