Disrupted Lipid Metabolism in Multiple Sclerosis: A Role for Liver X Receptors?

Pineda-Torra, Inés; Siddique, Sherrice; Waddington, Kirsty E.; Farrell, Rachel; Jury, Elizabeth C.

doi:10.3389/fendo.2021.639757

Cited by 34 publications

(22 citation statements)

References 130 publications

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“…Recent studies point to a lipid dysregulation in MS patients and cognitive dysfunction, in which LXRs gained attention as a potential target [755][756][757] since LXR activation ameliorated disease severity in experimental autoimmune encephalomyelitis (EAE) models [758,759].…”

Section: Multiple Sclerosismentioning

confidence: 99%

APOE in the bullseye of neurodegenerative diseases: impact of the APOE genotype in Alzheimer’s disease pathology and brain diseases

Fernández-Calle

Konings

Frontiñán-Rubio

et al. 2022

Mol Neurodegeneration

100

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ApoE is the major lipid and cholesterol carrier in the CNS. There are three major human polymorphisms, apoE2, apoE3, and apoE4, and the genetic expression of APOE4 is one of the most influential risk factors for the development of late-onset Alzheimer's disease (AD). Neuroinflammation has become the third hallmark of AD, together with Amyloid-β plaques and neurofibrillary tangles of hyperphosphorylated aggregated tau protein. This review aims to broadly and extensively describe the differential aspects concerning apoE. Starting from the evolution of apoE to how APOE's single-nucleotide polymorphisms affect its structure, function, and involvement during health and disease. This review reflects on how APOE's polymorphisms impact critical aspects of AD pathology, such as the neuroinflammatory response, particularly the effect of APOE on astrocytic and microglial function and microglial dynamics, synaptic function, amyloid-β load, tau pathology, autophagy, and cell–cell communication. We discuss influential factors affecting AD pathology combined with the APOE genotype, such as sex, age, diet, physical exercise, current therapies and clinical trials in the AD field. The impact of the APOE genotype in other neurodegenerative diseases characterized by overt inflammation, e.g., alpha- synucleinopathies and Parkinson's disease, traumatic brain injury, stroke, amyotrophic lateral sclerosis, and multiple sclerosis, is also addressed. Therefore, this review gathers the most relevant findings related to the APOE genotype up to date and its implications on AD and CNS pathologies to provide a deeper understanding of the knowledge in the APOE field.

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Section: Multiple Sclerosismentioning

confidence: 99%

APOE in the bullseye of neurodegenerative diseases: impact of the APOE genotype in Alzheimer’s disease pathology and brain diseases

Fernández-Calle

Konings

Frontiñán-Rubio

et al. 2022

Mol Neurodegeneration

100

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“…Altered fatty acid metabolism and reduced cholesterol and cholesteryl esters were observed. There has been evidence indicating that changes in lipid metabolism, such as those in cholesterol, sphingolipids, and fatty acids, have a role not only in the aetiology of neurodegenerative diseases like MS but also as indicators of the disease’s occurrence and development (46). Unusual lipid-mediated communication in immune cells is one theory that could explain the aetiology of MS (47).…”

Section: Discussionmentioning

confidence: 99%

Developing a blood cell-based diagnostic test for myalgic encephalomyelitis/chronic fatigue syndrome using peripheral blood mononuclear cells

Lodge

Kingdon

et al. 2023

Preprint

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A blood-based diagnostic test for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and multiple sclerosis (MS) would be of great value in both conditions, facilitating more accurate and earlier diagnosis, helping with current treatment delivery, and supporting the development of new therapeutics. Here we use Raman micro-spectroscopy to examine differences between the spectral profiles of blood cells of ME/CFS, MS and healthy controls. We were able to discriminate the three groups using ensemble classification models with high levels of accuracy (91%) with the additional ability to distinguish mild, moderate, and severe ME/CFS patients from each other (84%). To our knowledge, this is the first research using Raman micro-spectroscopy to discriminate specific subgroups of ME/CFS patients on the basis of their symptom severity. Specific Raman peaks linked with the different disease types with the potential in further investigations to provide insights into biological changes associated with the different conditions.

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“…Neuronal and axonal degeneration leading to disability, which is an important neurodegenerative marker of MS, is closely associated with oxidative damage [ 60 ]. Neurons predominantly express N-methyl-D-aspartic acid (NMDA) receptors in the CNS.…”

Section: Oxidative Stress In the Cns Of Patients With Msmentioning

confidence: 99%

Potential Utility of Natural Products against Oxidative Stress in Animal Models of Multiple Sclerosis

Zha

Liu

et al. 2022

Antioxidants

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Multiple sclerosis (MS) is an autoimmune-mediated degenerative disease of the central nervous system (CNS) characterized by immune cell infiltration, demyelination and axonal injury. Oxidative stress-induced inflammatory response, especially the destructive effect of immune cell-derived free radicals on neurons and oligodendrocytes, is crucial in the onset and progression of MS. Therefore, targeting oxidative stress-related processes may be a promising preventive and therapeutic strategy for MS. Animal models, especially rodent models, can be used to explore the in vivo molecular mechanisms of MS considering their similarity to the pathological processes and clinical signs of MS in humans and the significant oxidative damage observed within their CNS. Consequently, these models have been used widely in pre-clinical studies of oxidative stress in MS. To date, many natural products have been shown to exert antioxidant effects to attenuate the CNS damage in animal models of MS. This review summarized several common rodent models of MS and their association with oxidative stress. In addition, this review provides a comprehensive and concise overview of previously reported natural antioxidant products in inhibiting the progression of MS.

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Disrupted Lipid Metabolism in Multiple Sclerosis: A Role for Liver X Receptors?

Cited by 34 publications

References 130 publications

APOE in the bullseye of neurodegenerative diseases: impact of the APOE genotype in Alzheimer’s disease pathology and brain diseases

APOE in the bullseye of neurodegenerative diseases: impact of the APOE genotype in Alzheimer’s disease pathology and brain diseases

Developing a blood cell-based diagnostic test for myalgic encephalomyelitis/chronic fatigue syndrome using peripheral blood mononuclear cells

Potential Utility of Natural Products against Oxidative Stress in Animal Models of Multiple Sclerosis

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