Targeting TNF: a therapeutic strategy for Alzheimer's disease

• Published in: Drug discovery today Vol. 19; no. 11; pp. 1822 - 1827
• Main Authors: Cheng, Xin, Shen, Yong, Li, Rena
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.11.2014
• Subjects: Alzheimer Disease - drug therapy; Alzheimer Disease - genetics; Alzheimer Disease - metabolism; Animals; Brain - metabolism; Humans; Receptors, Tumor Necrosis Factor - metabolism; Receptors, Tumor Necrosis Factor, Type I - metabolism; Signal Transduction; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 1359-6446; 1878-5832
• DOI: 10.1016/j.drudis.2014.06.029

•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.