TNF and neurodegenerative disease: As PrPsc aggregates progressively form over time, they further induce inevitably fatal neurodegenerative disease conditions, including neuroinflammation, which is typically discernable by massive microglial activation and proliferation and the subsequent and self-reinforcing upregulation of cytokines, such as TNF-alpha (TNFα), interleukin 1 alpha (IL-1α) and glial fibrillary acidic protein (GFAP) as well as astrogliosis accompanied by multiple additional pathogenic alterations in the neuronal transcriptome [25,59,67,85,86,96].