Activation of RIPK1 can initiate a degenerative signaling loop which promotes neuroinflammation in the CNS. Microglial RIPK1 regulates the necroptosis of oligodendrocytes by driving the cell-autonomous expression of proinflammatory cytokines, and leads to demyelination and axonal degeneration. Neurons with damaged mitochondria and lysosomes may undergo necroptosis. In turn, the necroptosis of either oligodendrocytes or neurons produce damage associated molecules (DAMPs) resulting in progressive inflammatory in the brain to promote the progression of neurodegenerative disease.