Serum phospholipidomics reveals altered lipid profile and promising biomarkers in multiple sclerosis

Ferreira, Helena Beatriz; Melo, Tânia; Monteiro, Aílton Rocha; Paiva, Artur; Domingues, Pedro; Domingues, M. Rosário M.

doi:10.1016/j.abb.2020.108672

Cited by 41 publications

(30 citation statements)

References 48 publications

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“…In MS, mitochondrial dysfunction drives neuroinflammation, likely via an oxidative stress mechanism ( Bargiela and Chinnery, 2019 ). While the plasmalogen-specific literature surrounding MS is inchoate, recently a marked decrease in plasmalogen (PC-Pls and PE-Pls) content in the serum of MS patients experiencing both remission and relapse of MS has been reported ( Table 2 ) ( Ferreira et al, 2021 ). It has been proposed that this decline in plasmalogen species in MS patients might have various causes, including (i) increased immune system stress contributing to the reduction of plasmalogen via its oxidation, and (ii) MS-related demyelination, which might also contribute to plasmalogen loss as the myelin sheath is enriched in plasmalogen species ( Ferreira et al, 2021 ).…”

Section: Lowered Plasmalogen Levels In Pathophysiological Conditionsmentioning

confidence: 99%

Plasmalogens and Chronic Inflammatory Diseases

2021

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It is becoming widely acknowledged that lipids play key roles in cellular function, regulating a variety of biological processes. Lately, a subclass of glycerophospholipids, namely plasmalogens, has received increased attention due to their association with several degenerative and metabolic disorders as well as aging. All these pathophysiological conditions involve chronic inflammatory processes, which have been linked with decreased levels of plasmalogens. Currently, there is a lack of full understanding of the molecular mechanisms governing the association of plasmalogens with inflammation. However, it has been shown that in inflammatory processes, plasmalogens could trigger either an anti- or pro-inflammation response. While the anti-inflammatory response seems to be linked to the entire plasmalogen molecule, its pro-inflammatory response seems to be associated with plasmalogen hydrolysis, i.e., the release of arachidonic acid, which, in turn, serves as a precursor to produce pro-inflammatory lipid mediators. Moreover, as plasmalogens comprise a large fraction of the total lipids in humans, changes in their levels have been shown to change membrane properties and, therefore, signaling pathways involved in the inflammatory cascade. Restoring plasmalogen levels by use of plasmalogen replacement therapy has been shown to be a successful anti-inflammatory strategy as well as ameliorating several pathological hallmarks of these diseases. The purpose of this review is to highlight the emerging role of plasmalogens in chronic inflammatory disorders as well as the promising role of plasmalogen replacement therapy in the treatment of these pathologies.

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Section: Lowered Plasmalogen Levels In Pathophysiological Conditionsmentioning

confidence: 99%

Plasmalogens and Chronic Inflammatory Diseases

2021

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“…In the context of MS, particularly the progressive forms of this disease, it is worth to note that myelin is not only a major component of the white matter but is also present in grey matter [66], although in much smaller quantities. In multiple metabolomic studies, increased levels of CSF choline and altered plasma levels of certain phospholipids, particularly those containing choline, were detected in MS patients [67][68][69][70]. Metabolomic studies cannot identify the source of these alterations.…”

Section: Citicoline Should Be Evaluated In Msmentioning

confidence: 99%

Citicoline: A Candidate for Adjunct Treatment of Multiple Sclerosis

et al. 2021

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In remitting–relapsing multiple sclerosis (RR-MS), relapses are driven by autoreactive immune cells that enter the brain and spinal cord and damage myelin sheaths of axons in white and grey matter, whereas during remissions myelin is repaired by activated oligodendroglial cells. Disease-modifying therapies (DMTs) may either retard/attenuate myelin damage or promote/enhance/speed up myelin repair. Almost all currently approved DMTs inhibit myelin damage and are considerably toxic. Enhancement of myelin repair is considered an unmet medical need of MS patients. Citicoline, known for many years as a nootropic and neuroprotective drug and recently pronounced food supplement, has been found to be significantly efficacious in two complementary rodent models of MS, experimental autoimmune encephalomyelitis (EAE) and cuprizone-induced myelin toxicity. Moreover, citicoline treatment improves visual evoked potentials (VEPs) in glaucoma patients, which is relevant because VEP monitoring is frequently used as an indicator of remyelination in MS. Although over-the-counter availability of citicoline may impede its formal translation to the clinic of MS, evaluation of its efficacy for supporting remyelination in this disease is strongly indicated.

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“…Pls are also concentrated in specialized membranes, such as sarcolemma, myelin, and synaptic vesicles ( Post et al, 1988 ; Takamori et al, 2006 ; Poitelon et al, 2020 ). Reduced levels of PlsEtns have been found to be associated with aging ( Pradas et al, 2019 ) and several neurodegenerative diseases, including Alzheimer’s disease (AD) ( Guan et al, 1999 ; Han et al, 2001 ; Goodenowe et al, 2007 ; Wood 2010 ; Wood et al, 2015 ; Yamashita et al, 2016b ), Parkinson’s disease (PD) ( Dragonas et al, 2009 ; Fabelo et al, 2011 ; Xicoy et al, 2019 ), Niemann-Pick type C disease ( Schedin and Pavel 1997 ), multiple sclerosis (MS) ( Ferreira et al, 2021 ) and Zellweger syndrome ( Heymans et al, 1983 ).…”

Section: Introductionmentioning

confidence: 99%

Plasmalogens Eliminate Aging-Associated Synaptic Defects and Microglia-Mediated Neuroinflammation in Mice

Chen

Sun

et al. 2022

Front. Mol. Biosci.

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Neurodegeneration is a pathological condition in which nervous system or neuron losses its structure, function, or both leading to progressive neural degeneration. Growing evidence strongly suggests that reduction of plasmalogens (Pls), one of the key brain lipids, might be associated with multiple neurodegenerative diseases, including Alzheimer’s disease (AD). Plasmalogens are abundant members of ether-phospholipids. Approximately 1 in 5 phospholipids are plasmalogens in human tissue where they are particularly enriched in brain, heart and immune cells. In this study, we employed a scheme of 2-months Pls intragastric administration to aged female C57BL/6J mice, starting at the age of 16 months old. Noticeably, the aged Pls-fed mice exhibited a better cognitive performance, thicker and glossier body hair in appearance than that of aged control mice. The transmission electron microscopic (TEM) data showed that 2-months Pls supplementations surprisingly alleviate age-associated hippocampal synaptic loss and also promote synaptogenesis and synaptic vesicles formation in aged murine brain. Further RNA-sequencing, immunoblotting and immunofluorescence analyses confirmed that plasmalogens remarkably enhanced both the synaptic plasticity and neurogenesis in aged murine hippocampus. In addition, we have demonstrated that Pls treatment inhibited the age-related microglia activation and attenuated the neuroinflammation in the murine brain. These findings suggest for the first time that Pls administration might be a potential intervention strategy for halting neurodegeneration and promoting neuroregeneration.

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Serum phospholipidomics reveals altered lipid profile and promising biomarkers in multiple sclerosis

Cited by 41 publications

References 48 publications

Plasmalogens and Chronic Inflammatory Diseases

Plasmalogens and Chronic Inflammatory Diseases

Citicoline: A Candidate for Adjunct Treatment of Multiple Sclerosis

Plasmalogens Eliminate Aging-Associated Synaptic Defects and Microglia-Mediated Neuroinflammation in Mice

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