Targeting TNF: a therapeutic strategy for Alzheimer's disease

Tumor necrosis factor (TNF), a ligand cytokine, is involved in systemic inflammation. Apart from the well-known pharmacological effects of TNF inhibitors on autoimmune disorders, interest in the effects of TNF in neurodegenerative disorders such as Alzheimer disease (AD) is increasing. TNF and its type 1 receptor (TNFRI) are not only involved in AD-related brain neuroinflammation, but also contribute to amyloidogenesis via beta-secretase regulation, suggesting TNF as a promising candidate for future AD therapy. Although the potential adverse effects of TNF-based AD therapies have been of concerns, here we summarize recent discoveries relating to TNF and TNFRI-mediated signal transduction as potential therapeutic targets in AD pathology and clinical investigations.