Diverse pathways to neuronal necroptosis in Alzheimer's disease
File(s)
Accepted version
Author(s)
Jayaraman, Anusha
Reynolds, Richard
Type
Journal Article
Abstract
Necroptosis, or programmed necrosis, involves the kinase activity of receptor interacting kinases 1 and 3, the activation of the pseudokinase mixed lineage kinase domain-like and formation of a complex called the necrosome. It is one of the non-apoptotic cell death pathways that has gained interest in the recent years, especially as a neuronal cell death pathway occurring in Alzheimer's disease. In this review, we focus our discussion on the various molecular mechanisms that could trigger neuronal death through necroptosis and have been shown to play a role in Alzheimer's disease pathogenesis and neuroinflammation. We describe how each of these pathways, such as tumour necrosis factor signalling, reactive oxygen species, endosomal sorting complex, post-translational modifications and certain individual molecules, is dysregulated or activated in Alzheimer's disease, and how this dysregulation/activation could trigger necroptosis. At the cellular level, many of these molecular mechanisms and pathways may act in parallel to synergize with each other or inhibit one another, and changes in the balance between them may determine different cellular vulnerabilities at different disease stages. However, from a therapeutic standpoint, it remains unclear how best to target one or more of these pathways, given that such diverse pathways could all contribute to necroptotic cell death in Alzheimer's disease.
Date Issued
2022-11-01
Date Acceptance
2022-03-29
Citation
European Journal of Neuroscience, 2022, 56 (9), pp.5428-5441
ISSN
0953-816X
Publisher
Wiley
Start Page
5428
End Page
5441
Journal / Book Title
European Journal of Neuroscience
Volume
56
Issue
9
Copyright Statement
© 2022 Federation of European Neuroscience Societies and John Wiley & Sons Ltd. This is the peer reviewed version of the following article, which has been published in final form at https://onlinelibrary.wiley.com/doi/10.1111/ejn.15662. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.
Identifier
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000780400100001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Alzheimer's disease
apoptosis
CELL-DEATH
CEREBROSPINAL-FLUID
cytokines
ESCRT-III
GLUTAMATE TRANSPORTER
hippocampus
INFLAMMASOME ACTIVATION
Life Sciences & Biomedicine
MAMMALIAN TARGET
necroptosis
neuroinflammation
Neurosciences
Neurosciences & Neurology
NLRP3 INFLAMMASOME
Science & Technology
SIGNALING PATHWAY
TAU-PROTEIN
TNF
Publication Status
Published
Date Publish Online
2022-04-04