Astrocytes in multiple sclerosis and experimental autoimmune encephalomyelitis: Star-shaped cells illuminating the darkness of CNS autoimmunity

Yi, Wen-Jing; Schlüter, Dirk; Wang, Xu

doi:10.1016/j.bbi.2019.05.029

Cited by 53 publications

(45 citation statements)

References 257 publications

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“…Glutamate is the central nervous system's main excitatory neurotransmitter, but when present in excess it triggers a chain of negative reactions. Glutamate neurotoxicity's involvement in the pathogenesis of demyelination and neuronal and synaptic damage in MS has been demonstrated on numerous occasions [56]; activated immune cells and astrocytes release large amounts of glutamate, damaging myelin sheaths and axons [57,58], and changes in glutamate levels in these areas have been associated with the later stages of MS, episodes, and secondary progression. An imbalance in glutamate receptor levels and expression can also occur in earlier stages or even when no damage is observed in white matter with MRI.…”

Section: Discussionmentioning

confidence: 99%

Empirical Mode Decomposition-Based Filter Applied to Multifocal Electroretinograms in Multiple Sclerosis Diagnosis

Santiago

Castillo

García‐Martín

et al. 2019

Sensors

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As multiple sclerosis (MS) usually affects the visual pathway, visual electrophysiological tests can be used to diagnose it. The objective of this paper is to research methods for processing multifocal electroretinogram (mfERG) recordings to improve the capacity to diagnose MS. MfERG recordings from 15 early-stage MS patients without a history of optic neuritis and from 6 control subjects were examined. A normative database was built from the control subject signals. The mfERG recordings were filtered using empirical mode decomposition (EMD). The correlation with the signals in a normative database was used as the classification feature. Using EMD-based filtering and performance correlation, the mean area under the curve (AUC) value was 0.90. The greatest discriminant capacity was obtained in ring 4 and in the inferior nasal quadrant (AUC values of 0.96 and 0.94, respectively). Our results suggest that the combination of filtering mfERG recordings using EMD and calculating the correlation with a normative database would make mfERG waveform analysis applicable to assessment of multiple sclerosis in early-stage patients. Author Contributions: Conceptualization, E.G.-M., M.J.R., E.M.S.M., and L.B.; methodology, L.d.S., M.O.d.C., C.C., J.M.M., A.L., and B.C.; software, L.d.S., M.O.d.C., C.C., J.M.M., and A.L.; validation, L.d.S., M.O.d.C., C.C., J.M.M., and A.L.; formal Analysis, M.O.d.C. and J.M.M.; investigation, E.G.-M., M.J.R., E.M.S.M., and L.B.; resources, L.B. and E.G.-M.; data Curation, L.d.S., M.O.d.C., C.C., J.M.M., A.L., and B.C.; writing-original draft preparation, L.B., E.G.-M., and M.J.R.; writing-review and editing, L.B., E.G.-M., and M.J.R.; visualization, L.B. and E.G.-M.; supervision, L.B. and E.G.-M.; project administration, L.B. and E.G.-M.; funding acquisition, L.B. and E.G.-M. All authors have read and agreed to the published version of the manuscript.

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Section: Discussionmentioning

confidence: 99%

Empirical Mode Decomposition-Based Filter Applied to Multifocal Electroretinograms in Multiple Sclerosis Diagnosis

Santiago

Castillo

García‐Martín

et al. 2019

Sensors

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“…Both CNS homeostasis and neuroinflammation can be to a large extent controlled by CNS-resident cells such as microglia, a CNS-resident macrophage-like cell population, and astrocytes, the most abundant cells in the CNS. Microglia and astrocytes are emerging as crucial regulators of CNS autoimmunity, and their multi-faceted functions in MS and EAE have been summarized by other reviews [85,86]. The immune-regulating abilities of microglia and astrocytes are primarily ascribed to their responsiveness to cytokines secreted by infiltrating encephalitogenic T cells.…”

Section: Dubs Regulate Cns-resident Cells In Ms/eaementioning

confidence: 99%

“…Mice deficient of OTUB1 selectively in astrocytes do not show abnormalities under physiological conditions but develop more severe EAE [95]. Of note, astrocytes play both protective and detrimental roles in EAE [86]. However, according to the twowave theory of EAE development, astrocytes contribute to EAE, at least in the early stage, by producing leukocyterecruiting molecules [98].…”

Section: Otub1mentioning

confidence: 99%

Deubiquitinating enzymes (DUBs): DoUBle-edged swords in CNS autoimmunity

Ruan

Schlüter

Wang

2020

J Neuroinflammation

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Multiple sclerosis (MS) is the most common autoimmune disease of the CNS. The etiology of MS is still unclear but it is widely recognized that both genetic and environmental factors contribute to its pathogenesis. Immune signaling and responses are critically regulated by ubiquitination, a posttranslational modification that is promoted by ubiquitinating enzymes and inhibited by deubiquitinating enzymes (DUBs). Genome-wide association studies (GWASs) identified that polymorphisms in or in the vicinity of two human DUB genes TNFAIP3 and USP18 were associated with MS susceptibility. Studies with experimental autoimmune encephalomyelitis (EAE), an animal model of MS, have provided biological rationale for the correlation between these DUBs and MS. Additional studies have shown that other DUBs are also involved in EAE by controlling distinct cell populations. Therefore, DUBs are emerging as crucial regulators of MS/EAE and might become potential therapeutic targets for the clinical treatment of MS.

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“…17,97,[150][151][152][153] Vitamin D is a modulator of the immune system, 154,155 hence its mention here, and accumulating evidence suggests vitamin D deficiency is a risk factor for dysregulated Klotho-associated neurodegenerative diseases, the most noteworthy being MS. 9,27,52,97,102,150,152,153,[156][157][158] Multiple Sclerosis MS is an insidious progressive neurodegenerative disease characterized by demyelinated lesions throughout the brain, spinal cord, and optic nerve resulting from immune-mediated attacks against myelin. [159][160][161][162][163][164][165] It is the apotheosis of myelination disorders that affects *2.5 million people around the world [166][167][168] and currently there are no definitive cures. The standard of chronic care, after using steroids for acute episodes, centers on the use of disease modifying therapies (DMTs) that modulate an overactive immune response, such as antibodies against interferon, interleukin, or related T cell targets.…”

Section: Introductionmentioning

confidence: 99%

Klotho Pathways, Myelination Disorders, Neurodegenerative Diseases, and Epigenetic Drugs

Moos

Faller

Glavas

et al. 2020

BioResearch Open Access

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In this review we outline a rationale for identifying neuroprotectants aimed at inducing endogenous Klotho activity and expression, which is epigenetic action, by definition. Such an approach should promote remyelination and/or stimulate myelin repair by acting on mitochondrial function, thereby heralding a life-saving path forward for patients suffering from neuroinflammatory diseases. Disorders of myelin in the nervous system damage the transmission of signals, resulting in loss of vision, motion, sensation, and other functions depending on the affected nerves, currently with no effective treatment. Klotho genes and their single-pass transmembrane Klotho proteins are powerful governors of the threads of life and death, true to the origin of their name, Fates, in Greek mythology. Among its many important functions, Klotho is an obligatory co-receptor that binds, activates, and/or potentiates critical fibroblast growth factor activity. Since the discovery of Klotho a little over two decades ago, it has become ever more apparent that when Klotho pathways go awry, oxidative stress and mitochondrial dysfunction take over, and age-related chronic disorders are likely to follow. The physiological consequences can be wide ranging, potentially wreaking havoc on the brain, eye, kidney, muscle, and more. Central nervous system disorders, neurodegenerative in nature, and especially those affecting the myelin sheath, represent worthy targets for advancing therapies that act upon Klotho pathways. Current drugs for these diseases, even therapeutics that are disease modifying rather than treating only the symptoms, leave much room for improvement. It is thus no wonder that this topic has caught the attention of biomedical researchers around the world.

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Astrocytes in multiple sclerosis and experimental autoimmune encephalomyelitis: Star-shaped cells illuminating the darkness of CNS autoimmunity

Cited by 53 publications

References 257 publications

Empirical Mode Decomposition-Based Filter Applied to Multifocal Electroretinograms in Multiple Sclerosis Diagnosis

Empirical Mode Decomposition-Based Filter Applied to Multifocal Electroretinograms in Multiple Sclerosis Diagnosis

Deubiquitinating enzymes (DUBs): DoUBle-edged swords in CNS autoimmunity

Klotho Pathways, Myelination Disorders, Neurodegenerative Diseases, and Epigenetic Drugs

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