Journal
FRONTIERS IN NEUROSCIENCE
Volume 13, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fnins.2019.00049
Keywords
tumor necrosis factor; Alzheimer's disease; neurodegeneration; neuroprotection; agonists; antagonists
Categories
Funding
- ZonMW Deltaplan Dementie Memorabel and Alzheimer Nederland [733050815]
- Alzheimer Nederland [WE. 13-2015-19]
- NeuroSearch Antwerp
- Foundation MS Research Nederland [15 - 898 MS]
- China Scholarship Council (CSC) program [201607040062]
- ZonMW Deltaplan Dementie Memorabel
- Dutch Technology Foundation TTW part of the Netherlands Organization for Scientific Research (NWO) - Ministry of Economic Affairs
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Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia. Accumulating experimental evidence shows the important linkage between tumor necrosis factor-alpha (TNF) and AD, but the exact role of TNF in AD is still not completely understood. Although TNF-inhibitors are successfully used for treating several diseases, total inhibition of TNF can cause side effects, particularly in neurological diseases. This is attributed to the opposing roles of the two TNF receptors. TNF receptor 1 (TNFR1) predominantly mediates inflammatory and proapoptotic signaling pathways, whereas TNF receptor 2 (TNFR2) is neuroprotective and promotes tissue regeneration. Therefore, the specific activation of TNFR2 signaling, either by directly targeting TNFR2 via TNFR2 agonists or by blocking TNFR1 signaling with TNFR1-selective antagonists, seems a promising strategy for AD therapy. This mini-review discusses the involvement of TNFR2 and its signaling pathway in AD and outlines its potential application as therapeutic target. A better understanding of the function of TNFR2 may lead to the development of a treatment for AD.
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