Editing Tumor necrosis factor (section)

=== Neuroinflammation ===
In the [[central nervous system]], TNF is primarily produced by [[microglia]], a type of macrophage, but also by [[neurons]], [[endothelial cells]], and immune cells. Excessive TNF contributes to [[neuroinflammation]] by causing [[Excitotoxicity|excitotoxic]] neuronal cell death, increasing [[glutamate]] levels, activating microglial cells, and disrupting the [[blood–brain barrier]]. As a result, TNF is seen to play an important role in central nervous system disorders associated with neuroinflammation, including [[neurosarcoidosis]], [[multiple sclerosis]], [[Neuro-Behçet's disease]].<ref name="RoleOfTNFInCNS">{{cite journal | vauthors = Caldito NG | title = Role of tumor necrosis factor-alpha in the central nervous system: a focus on autoimmune disorders | journal = Frontiers in Immunology | date = July 2023 | volume = 14 | doi = 10.3389/fimmu.2023.1213448 | doi-access = free | pmid = 37483590 | pmc = 10360935 }}</ref>

Paradoxically, TNF-blockers can cause demyelination of neurons and worsen multiple sclerosis symptoms. This is believed to be due to the homeostatic role of TNF in the central nervous system, especially on neuron myelination via TNFR2. The selective blockade of TNFR1 has shown positive outcomes in animal models.<ref name="RoleOfTNFInCNS"/>

TNF-induced neuroinflammation has also been associated with [[Alzheimer's disease]], and is suspected to contribute to the [[Amyloid plaques|amyloid-β plaques]] and [[tau protein]] hyperphosphorylation found in the brains of Alzheimer's patients. TNF blockers have been associated with reduced risk of developing Alzheimer's. Some studies have shown TNF blockers to slightly improve cognition in Alzheimer's patients, though larger studies are needed. Since TNF blockers cannot pass through the blood–brain barrier, it is believed that reducing TNF levels across the body also reduces TNF levels within the brain.<ref name="pmid33016914">{{cite journal | vauthors = Torres-Acosta N, O'Keefe JH, O'Keefe EL, Isaacson R, Small G | title = Therapeutic Potential of TNF-α Inhibition for Alzheimer's Disease Prevention | journal = Journal of Alzheimer's Disease| volume = 78 | issue = 2 | pages = 619–626 | date = November 2020 | pmid = 33016914 | pmc = 7739965 | doi =  10.3233/JAD-200711 | doi-access = free }}</ref>