Could anionic LDL be a ligand for RAGE and TREM2 in addition to LOX-1 and thus exacerbate lung disease and dementia?
Could anionic LDL be a ligand for RAGE and TREM2 in addition to LOX-1 and thus exacerbate lung disease and dementia?
We recently highlighted the potential of protein glycation to generate anionic (electronegative) surfaces. We hypothesised that these anionic proteins are perceived by the innate immune system as arising from infection or damaged cell components, producing an inflammatory response within the lung involving the receptor RAGE. We now review two other pathologies linked to the innate immune response, cardiovascular disease and dementia that involve receptors LOX-1 and TREM2 respectively. Remarkable similarities in properties between RAGE, LOX-1 and TREM2 suggest that electronegative LDL may act as a pathogenic anionic ligand for all three receptors and exacerbate lung inflammation and dementia.
Cardiovascular disease, Dementia, LOX-1, RAGE, TREM2, lung inflammation and immunity, Lung inflammation
Birts, Charles N.
8689ddad-ba47-4ca6-82c5-001315dbd250
Wilton, David C.
4b995f66-ad6c-4d96-9179-c64f3b54466a
1 December 2023
Birts, Charles N.
8689ddad-ba47-4ca6-82c5-001315dbd250
Wilton, David C.
4b995f66-ad6c-4d96-9179-c64f3b54466a
Birts, Charles N. and Wilton, David C.
(2023)
Could anionic LDL be a ligand for RAGE and TREM2 in addition to LOX-1 and thus exacerbate lung disease and dementia?
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 1869 (8), [166837].
(doi:10.1016/j.bbadis.2023.166837).
Abstract
We recently highlighted the potential of protein glycation to generate anionic (electronegative) surfaces. We hypothesised that these anionic proteins are perceived by the innate immune system as arising from infection or damaged cell components, producing an inflammatory response within the lung involving the receptor RAGE. We now review two other pathologies linked to the innate immune response, cardiovascular disease and dementia that involve receptors LOX-1 and TREM2 respectively. Remarkable similarities in properties between RAGE, LOX-1 and TREM2 suggest that electronegative LDL may act as a pathogenic anionic ligand for all three receptors and exacerbate lung inflammation and dementia.
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Accepted/In Press date: 31 July 2023
e-pub ahead of print date: 5 August 2023
Published date: 1 December 2023
Additional Information:
Funding Information:
We would like to thank Professor Mohammad Akhtar FRS for his support and Professor Dennis Vance for stimulating the writing of this paper. Charles Birts is supported by the Against Breast Cancer Lectureship and gratefully acknowledges a programme grant from Against Breast Cancer ( www.againstbreastcancer.org.uk ; UK Charity 1121258 ). For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.
Publisher Copyright:
© 2023 The Authors
Keywords:
Cardiovascular disease, Dementia, LOX-1, RAGE, TREM2, lung inflammation and immunity, Lung inflammation
Identifiers
Local EPrints ID: 481399
URI: http://eprints.soton.ac.uk/id/eprint/481399
ISSN: 0925-4439
PURE UUID: 5d18483d-63b1-498e-8aff-861cfed79cdc
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Date deposited: 25 Aug 2023 16:34
Last modified: 18 Mar 2024 02:56
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