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Cholesterol Dysregulation in Multiple Sclerosis: Implications for Pathogenesis and Opportunities for Monitoring and Treating Progressive Disease / KRISTEN HAWKINS

Swansea University Author: KRISTEN HAWKINS

  • E-Thesis – open access under embargo until: 1st January 2025

DOI (Published version): 10.23889/SUthesis.66037

Abstract

Multiple sclerosis (MS) is characterised by demyelination, neuroinflammation and neurodegeneration that contributes to a progressively worsening condition over time. Ongoing, chronic demyelination is an important hallmark of MS pathobiology; however the underlying drivers of progression have not bee...

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Published: Swansea University, Wales, UK 2024
Institution: Swansea University
Degree level: Doctoral
Degree name: Ph.D
Supervisor: Howell, O. W.; Griffiths, W. J.; and Wang, Y.
URI: https://cronfa.swan.ac.uk/Record/cronfa66037
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first_indexed 2024-04-11T11:31:30Z
last_indexed 2024-04-11T11:31:30Z
id cronfa66037
recordtype RisThesis
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spelling v2 66037 2024-04-11 Cholesterol Dysregulation in Multiple Sclerosis: Implications for Pathogenesis and Opportunities for Monitoring and Treating Progressive Disease 4d68c146dfb2c32f9f2a8c515cefd01f KRISTEN HAWKINS KRISTEN HAWKINS true false 2024-04-11 Multiple sclerosis (MS) is characterised by demyelination, neuroinflammation and neurodegeneration that contributes to a progressively worsening condition over time. Ongoing, chronic demyelination is an important hallmark of MS pathobiology; however the underlying drivers of progression have not been fully elucidated. Microglia mediate demyelination and contribute to continued lesion expansion.Phagocytosis and processing of myelin by microglia and macrophages results in the release of myelin-lipids – including cholesterol, and dysregulation of cholesterol homeostasis may drive a damaging microglial/macrophage response. The oxidised metabolites of cholesterol – oxysterols – are important ligands implicated in myelination, neuroinflammation and neuron survival and may represent a druggable target. Little is known about the abundance and location of cholesterol and the oxysterols in the MS brain, or how their dysregulation may contribute to a worsening progressive MS. E-Thesis Swansea University, Wales, UK Progressive multiple sclerosis, cholesterol, oxysterols 23 2 2024 2024-02-23 10.23889/SUthesis.66037 Part of this thesis has been redacted to protect personal information COLLEGE NANME COLLEGE CODE Swansea University Howell, O. W.; Griffiths, W. J.; and Wang, Y. Doctoral Ph.D MS Society 2024-06-21T12:36:21.8780294 2024-04-11T12:21:08.8488525 Faculty of Medicine, Health and Life Sciences School of Health and Social Care - Public Health KRISTEN HAWKINS 1 Under embargo Under embargo 2024-06-21T12:32:06.2167688 Output 9715707 application/pdf E-Thesis – open access true 2025-01-01T00:00:00.0000000 Copyright: The Author, Kristen Hawkins, 2023 true eng
title Cholesterol Dysregulation in Multiple Sclerosis: Implications for Pathogenesis and Opportunities for Monitoring and Treating Progressive Disease
spellingShingle Cholesterol Dysregulation in Multiple Sclerosis: Implications for Pathogenesis and Opportunities for Monitoring and Treating Progressive Disease
KRISTEN HAWKINS
title_short Cholesterol Dysregulation in Multiple Sclerosis: Implications for Pathogenesis and Opportunities for Monitoring and Treating Progressive Disease
title_full Cholesterol Dysregulation in Multiple Sclerosis: Implications for Pathogenesis and Opportunities for Monitoring and Treating Progressive Disease
title_fullStr Cholesterol Dysregulation in Multiple Sclerosis: Implications for Pathogenesis and Opportunities for Monitoring and Treating Progressive Disease
title_full_unstemmed Cholesterol Dysregulation in Multiple Sclerosis: Implications for Pathogenesis and Opportunities for Monitoring and Treating Progressive Disease
title_sort Cholesterol Dysregulation in Multiple Sclerosis: Implications for Pathogenesis and Opportunities for Monitoring and Treating Progressive Disease
author_id_str_mv 4d68c146dfb2c32f9f2a8c515cefd01f
author_id_fullname_str_mv 4d68c146dfb2c32f9f2a8c515cefd01f_***_KRISTEN HAWKINS
author KRISTEN HAWKINS
author2 KRISTEN HAWKINS
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publishDate 2024
institution Swansea University
doi_str_mv 10.23889/SUthesis.66037
college_str Faculty of Medicine, Health and Life Sciences
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hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str School of Health and Social Care - Public Health{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}School of Health and Social Care - Public Health
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description Multiple sclerosis (MS) is characterised by demyelination, neuroinflammation and neurodegeneration that contributes to a progressively worsening condition over time. Ongoing, chronic demyelination is an important hallmark of MS pathobiology; however the underlying drivers of progression have not been fully elucidated. Microglia mediate demyelination and contribute to continued lesion expansion.Phagocytosis and processing of myelin by microglia and macrophages results in the release of myelin-lipids – including cholesterol, and dysregulation of cholesterol homeostasis may drive a damaging microglial/macrophage response. The oxidised metabolites of cholesterol – oxysterols – are important ligands implicated in myelination, neuroinflammation and neuron survival and may represent a druggable target. Little is known about the abundance and location of cholesterol and the oxysterols in the MS brain, or how their dysregulation may contribute to a worsening progressive MS.
published_date 2024-02-23T12:36:20Z
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score 11.012678

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