Plasmalogen Replacement Therapy

Bozelli, José Carlos; Epand, Richard M.

doi:10.3390/membranes11110838

Cited by 23 publications

(12 citation statements)

References 124 publications

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“…Plasmalogen enhancement in isolated cell studies protects cells from oxidative stress ( Zoeller et al, 1999 ). Additionally, several studies have investigated plasmalogen precursors as a potential treatment in inflammatory diseases ( Bozelli and Epand, 2021 ; Paul et al, 2021 ). Enhancing plasmalogen levels is difficult since dietary consumption of plasmalogens is reduced due to the acidic environment of the gastrointestinal tract.…”

Section: Discussionmentioning

confidence: 99%

Plasmalogen Loss in Sepsis and SARS-CoV-2 Infection

Pike

McGuffee

Geerling

et al. 2022

Front. Cell Dev. Biol.

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Plasmalogens are plasma-borne antioxidant phospholipid species that provide protection as cellular lipid components during cellular oxidative stress. In this study we investigated plasma plasmalogen levels in human sepsis as well as in rodent models of infection. In humans, levels of multiple plasmenylethanolamine molecular species were decreased in septic patient plasma compared to control subject plasma as well as an age-aligned control subject cohort. Additionally, lysoplasmenylcholine levels were significantly decreased in septic patients compared to the control cohorts. In contrast, plasma diacyl phosphatidylethanolamine and phosphatidylcholine levels were elevated in septic patients. Lipid changes were also determined in rats subjected to cecal slurry sepsis. Plasma plasmenylcholine, plasmenylethanolamine, and lysoplasmenylcholine levels were decreased while diacyl phosphatidylethanolamine levels were increased in septic rats compared to control treated rats. Kidney levels of lysoplasmenylcholine as well as plasmenylethanolamine molecular species were decreased in septic rats. Interestingly, liver plasmenylcholine and plasmenylethanolamine levels were increased in septic rats. Since COVID-19 is associated with sepsis-like acute respiratory distress syndrome and oxidative stress, plasmalogen levels were also determined in a mouse model of COVID-19 (intranasal inoculation of K18 mice with SARS-CoV-2). 3 days following infection, lung infection was confirmed as well as cytokine expression in the lung. Multiple molecular species of lung plasmenylcholine and plasmenylethanolamine were decreased in infected mice. In contrast, the predominant lung phospholipid, dipalmitoyl phosphatidylcholine, was not decreased following SARS-CoV-2 infection. Additionally total plasmenylcholine levels were decreased in the plasma of SARS-CoV-2 infected mice. Collectively, these data demonstrate the loss of plasmalogens during both sepsis and SARS-CoV-2 infection. This study also indicates plasma plasmalogens should be considered in future studies as biomarkers of infection and as prognostic indicators for sepsis and COVID-19 outcomes.

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Section: Discussionmentioning

confidence: 99%

Plasmalogen Loss in Sepsis and SARS-CoV-2 Infection

Pike

McGuffee

Geerling

et al. 2022

Front. Cell Dev. Biol.

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“…In conclusion, we propose that plasmalogens supplementation together with anti-PAF enriched food, such as the Mediterranean diet ( Tsoupras et al, 2018 ; Detopoulou et al, 2021 ), may provide an alternative strategy ( Bozelli and Epand, 2021 ) in inflammatory disease prevention and treatment through rebalancing of the inflammatory mediators and radicals, consequently return or regain system homeostasis.…”

Section: Discussionmentioning

confidence: 99%

“…Plasmalogen supplementations have been reported to improve cognition ( Hossain et al, 2018 ) and inhibit oxidative damage, neuro-inflammation and apoptosis ( Che et al, 2018 ; Bozelli et al, 2021 ). Restoring plasmalogens levels has been achieved by the use of plasmalogen replacement therapy ( Bozelli and Epand, 2021 ), which turned out to be a successful way to restore plasmalogen level as well as to improve diseased conditions via the potential anti-inflammatory property of plasmalogens ( Bozelli et al, 2021 ).…”

Section: Significance Of Plasmalogens As Bioactive Vinyl-ether Lipidsmentioning

confidence: 99%

Plasmalogenic Lipid Analogs as Platelet-Activating Factor Antagonists: A Potential Novel Class of Anti-inflammatory Compounds

Rong

Wang

Angelova

et al. 2022

Front. Cell Dev. Biol.

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Plasmalogens and Platelet-Activating Factor (PAF) are both bioactive ether phospholipids. Whereas plasmalogens are recognized for their important antioxidant function and modulatory role in cell membrane structure and dynamics, PAF is a potent pro-inflammatory lipid mediator known to have messenger functions in cell signaling and inflammatory response. The relationship between these two types of lipids has been rarely studied in terms of their metabolic interconversion and reciprocal modulation of the pro-inflammation/anti-inflammation balance. The vinyl-ether bonded plasmalogen lipid can be can be the lipid sources for the precursor of the biosynthesis of ether-bonded PAF. In this opinion paper, we suggest a potential role of plasmalogenic analogs of PAF as modulators and PAF antagonists (anti-PAF). We discuss that the metabolic interconversion of these two lipid kinds may be explored towards the development of efficient preventive and relief strategies against PAF-mediated pro-inflammation. We propose that plasmalogen analogs, acting as anti-PAF, may be considered as a new class of bioactive anti-inflammatory drugs. Despite of the scarcity of available experimental data, the competition between PAF and its natural plasmalogenic analogs for binding to the PAF receptor (PAF-R) can be proposed as a mechanistic model and potential therapeutic perspective against multiple inflammatory diseases (e.g., cardiovascular and neurodegenerative disorders, diabetes, cancers, and various manifestations in coronavirus infections such as COVID-19).

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“…The reduced level of plasmalogens has been commonly observed in the patients suffering from neurodegenerative disorders and appears to meet Bradford Hill criteria for causal association with neurodegeneration to a considerable extent ( Senanayake and Goodenowe 2019 ). Moreover, plasmalogen replacement therapy (PRT) has been shown to be a successful way to restore plasmalogen levels as well as to ameliorate pathological phenotypes ( Bozelli and Epand 2021 ), and an increasing number of studies suggests that plasmalogens may serve as potential therapeutic intervention for multiple neurodegenerative diseases, including AD and PD ( Fujino et al, 2017 ; Yamashita et al, 2017 ; Bourque et al, 2018 ; Fujino et al, 2018 ; Nadeau et al, 2019 ; Mawatari et al, 2020 ). These reports all point to a fact that the significance of plasmalogens in neuro-degeneration and neuro-regeneration.…”

Section: Discussionmentioning

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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Plasmalogen Replacement Therapy

Cited by 23 publications

References 124 publications

Plasmalogen Loss in Sepsis and SARS-CoV-2 Infection

Plasmalogen Loss in Sepsis and SARS-CoV-2 Infection

Plasmalogenic Lipid Analogs as Platelet-Activating Factor Antagonists: A Potential Novel Class of Anti-inflammatory Compounds

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

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