Version 1
: Received: 3 April 2024 / Approved: 4 April 2024 / Online: 4 April 2024 (06:04:04 CEST)
How to cite:
Alshaibi, R.; Ekanayake, K.; Barlow, E.; Mohamed, A. A.; Lucke-Wold, B. The Role of Tnf and Soluble Tnf Receptors (TNFR1/2) as Therapeutic Targets for Inflammation Secondary to Intracerebral Stroke and Hemorrhage. Preprints2024, 2024040337. https://doi.org/10.20944/preprints202404.0337.v1
Alshaibi, R.; Ekanayake, K.; Barlow, E.; Mohamed, A. A.; Lucke-Wold, B. The Role of Tnf and Soluble Tnf Receptors (TNFR1/2) as Therapeutic Targets for Inflammation Secondary to Intracerebral Stroke and Hemorrhage. Preprints 2024, 2024040337. https://doi.org/10.20944/preprints202404.0337.v1
Alshaibi, R.; Ekanayake, K.; Barlow, E.; Mohamed, A. A.; Lucke-Wold, B. The Role of Tnf and Soluble Tnf Receptors (TNFR1/2) as Therapeutic Targets for Inflammation Secondary to Intracerebral Stroke and Hemorrhage. Preprints2024, 2024040337. https://doi.org/10.20944/preprints202404.0337.v1
APA Style
Alshaibi, R., Ekanayake, K., Barlow, E., Mohamed, A. A., & Lucke-Wold, B. (2024). The Role of Tnf and Soluble Tnf Receptors (TNFR1/2) as Therapeutic Targets for Inflammation Secondary to Intracerebral Stroke and Hemorrhage. Preprints. https://doi.org/10.20944/preprints202404.0337.v1
Chicago/Turabian Style
Alshaibi, R., Ali Ahmed Mohamed and Brandon Lucke-Wold. 2024 "The Role of Tnf and Soluble Tnf Receptors (TNFR1/2) as Therapeutic Targets for Inflammation Secondary to Intracerebral Stroke and Hemorrhage" Preprints. https://doi.org/10.20944/preprints202404.0337.v1
Abstract
Most neurodegenerative diseases, including Alzheimer's disease, ischemic stroke, subarachnoid hemorrhage, and intracerebral hemorrhage are associated with inflammation. Tumor necrosis factor (TNF) is a pleiotropic pro-inflammatory cytokine that regulates cerebral infarction in stroke pathology, and its action is influenced by the bioavailability of its membrane-bound receptors, TNFR1 and TNFR2, and microglial activation. During the initial onset of these diseases, the soluble variant of the cytokine presents with prolonged and excessive activation of TNFR1, resulting in cell death and long-term neurological impairments. Therapeutic interventions for neurodegenerative diseases have targeted TNF to limit the onset of neuroinflammation. First-generation therapeutics have been demonstrated to inhibit membrane-bound TNF to TNFR2 receptor binding, resulting in severe side effects such as infections and cancer. As such, second-generation drugs, including XPro1595, have been developed to selectively inhibit soluble TNF and impede the effects of TNFR1 while still allowing for TNFR2 activation. Early results in murine TBI models demonstrate reduced glial reactivity by 50%, reduced dendritic degeneration by 30%, increased plasticity by 15%, and improved functional outcomes by 20% post-TBI. This scoping review of TNF receptors in various neurodegenerative diseases seeks to evaluate current and future therapeutic strategies as well as highlight potential strategies to eliminate confounding variables present in the current literature.
Medicine and Pharmacology, Neuroscience and Neurology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
