Fig. 2

Feedback loops involved in TNFα pathway related to neuroinflammation. The pathway depicts neuroinflammation induced production and release of TNFα from both microglia and astrocytes that could lead to dopaminergic cell death. Microglial release of TNFα caused its own release and initiated excess glutamate production. Excess TNFα kept microglia in the active state, which led to cellular imbalance of TNFα and glutamate. Glutamate bound to its microglial receptor and induced excess TNFα release. This prolonged activation in chronic inflammation led to rapid increase in glutamate, TNFα and other cellular factors which resulted in the damage of nearby neurons. Activated microglia also released TNFα that stimulated its own release. This initiated the production of excess extracellular glutamate that in turn induced release of TNFα. In neurons, TNFα triggers excess calcium influx which initiates pro-apoptotic factors and led to cell death. The cross-talk between the dying neuron and microglia maintained glial cells in an active state, leading to the release of TNFα