Article ID Journal Published Year Pages File Type
2079939 Drug Discovery Today 2014 6 Pages PDF
Abstract

•TNFα biosynthesis, TNF receptors, and signaling.•Neurotoxicity of TNFα in the brain.•TNFα receptor signaling-related neuron death and neuroprotection.•TNF receptors and Alzheimer disease, including signaling pathways in APP processing, Aβ, and genetic risk of AD.•Current status of anti-TNFα therapy in clinics and possible drug candidates for AD.

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 β-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.

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