Diverse pathways to neuronal necroptosis in Alzheimer's disease
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...
| Main Authors: | , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2022
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| Online Access: | https://hdl.handle.net/10356/162449 |
| _version_ | 1811679035757953024 |
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| author | Jayaraman, Anusha Reynolds, Richard |
| author2 | Lee Kong Chian School of Medicine (LKCMedicine) |
| author_facet | Lee Kong Chian School of Medicine (LKCMedicine) Jayaraman, Anusha Reynolds, Richard |
| author_sort | Jayaraman, Anusha |
| collection | NTU |
| description | 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. |
| first_indexed | 2024-10-01T03:02:45Z |
| format | Journal Article |
| id | ntu-10356/162449 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T03:02:45Z |
| publishDate | 2022 |
| record_format | dspace |
| spelling | ntu-10356/1624492022-10-19T05:46:50Z Diverse pathways to neuronal necroptosis in Alzheimer's disease Jayaraman, Anusha Reynolds, Richard Lee Kong Chian School of Medicine (LKCMedicine) Centre for Molecular Neuropathology Science::Medicine Alzheimer’s Disease Apoptosis 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. Nanyang Technological University This work was supported by an LKCMedicine Strategic Academic Initiative to RR. 2022-10-19T05:46:50Z 2022-10-19T05:46:50Z 2022 Journal Article Jayaraman, A. & Reynolds, R. (2022). Diverse pathways to neuronal necroptosis in Alzheimer's disease. European Journal of Neuroscience, 1-14. https://dx.doi.org/10.1111/ejn.15662 0953-816X https://hdl.handle.net/10356/162449 10.1111/ejn.15662 35377966 2-s2.0-85128304767 1 14 en European Journal of Neuroscience © 2022 Federation of European Neuroscience Societies and John Wiley & Sons Ltd. All rights reserved. |
| spellingShingle | Science::Medicine Alzheimer’s Disease Apoptosis Jayaraman, Anusha Reynolds, Richard Diverse pathways to neuronal necroptosis in Alzheimer's disease |
| title | Diverse pathways to neuronal necroptosis in Alzheimer's disease |
| title_full | Diverse pathways to neuronal necroptosis in Alzheimer's disease |
| title_fullStr | Diverse pathways to neuronal necroptosis in Alzheimer's disease |
| title_full_unstemmed | Diverse pathways to neuronal necroptosis in Alzheimer's disease |
| title_short | Diverse pathways to neuronal necroptosis in Alzheimer's disease |
| title_sort | diverse pathways to neuronal necroptosis in alzheimer s disease |
| topic | Science::Medicine Alzheimer’s Disease Apoptosis |
| url | https://hdl.handle.net/10356/162449 |
| work_keys_str_mv | AT jayaramananusha diversepathwaystoneuronalnecroptosisinalzheimersdisease AT reynoldsrichard diversepathwaystoneuronalnecroptosisinalzheimersdisease |