Mitochondria, Oxidative Stress, cAMP Signalling and Apoptosis: A Crossroads in Lymphocytes of Multiple Sclerosis, a Possible Role of Nutraceutics

Signorile, Anna; Ferretta, Anna; Ruggieri, Maddalena; Paolicelli, Damiano; Lattanzio, Paolo; Trojano, María; Rasmo, Domenico De

doi:10.3390/antiox10010021

Cited by 29 publications

(17 citation statements)

References 191 publications

(149 reference statements)

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“…In general, accumulating studies have proven that microglia show an anti-inflammatory phenotype and protect MNs at the onset of the disease, while end-stage microglia shift to a proinflammatory phenotype and aggravate the neurodegeneration of MNs in ALS ( Liu et al, 2021 ; Masrori et al, 2022 ). Astrocytes are the most common glial cells in the brain, maintain the CNS barriers ( Signorile et al, 2021 ), secrete neurotrophic and neuroprotective factors, regulate neurotransmitter uptake and recycling, and promote neurogenesis ( Gharbi et al, 2020 ). Studies have identified a role for astrocytes as immune modulators, as they may control the activation, migration, and proliferation of microglia ( Sunnemark et al, 2005 ; Ouali et al, 2018 ).…”

Section: Major Changes Of Resident Immune Cells In Amyotrophic Latera...mentioning

confidence: 99%

Neuroimmune Crosstalk Between the Peripheral and the Central Immune System in Amyotrophic Lateral Sclerosis

Cai

et al. 2022

Front. Aging Neurosci.

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Amyotrophic lateral sclerosis (ALS) is a fatal disease characterized by the degeneration and death of motor neurons. Systemic neuroinflammation contributes to the pathogenesis of ALS. The proinflammatory milieu depends on the continuous crosstalk between the peripheral immune system (PIS) and central immune system (CIS). Central nervous system (CNS) resident immune cells interact with the peripheral immune cells via immune substances. Dysfunctional CNS barriers, including the blood–brain barrier, and blood–spinal cord barrier, accelerate the inflammatory process, leading to a systemic self-destructive cycle. This review focuses on the crosstalk between PIS and CIS in ALS. Firstly, we briefly introduce the cellular compartments of CIS and PIS, respectively, and update some new understanding of changes specifically occurring in ALS. Then, we will review previous studies on the alterations of the CNS barriers, and discuss their crucial role in the crosstalk in ALS. Finally, we will review the moveable compartments of the crosstalk, including cytokines, chemokines, and peripheral immune cells which were found to infiltrate the CNS, highlighting the interaction between PIS and CIS. This review aims to provide new insights into pathogenic mechanisms and innovative therapeutic approaches for ALS.

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Section: Major Changes Of Resident Immune Cells In Amyotrophic Latera...mentioning

confidence: 99%

Neuroimmune Crosstalk Between the Peripheral and the Central Immune System in Amyotrophic Lateral Sclerosis

Cai

et al. 2022

Front. Aging Neurosci.

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“…Another important pathway where metabolites and genes converge is the cAMP signaling pathway. Mitochondrial stress, oxidative stress, and the cAMP signaling pathway nexus [ 50 ] appear to be correlated in heat-stressed granulosa cells [ 3 , 4 ]. Furthermore, the cAMP signaling pathway activates complex signaling involving the MAPK pathway, which can ultimately promote DNA damage and cell senescence [ 51 ].…”

Section: Discussionmentioning

confidence: 99%

Joint Transcriptome and Metabolome Analysis Prevails the Biological Mechanisms Underlying the Pro-Survival Fight in In Vitro Heat-Stressed Granulosa Cells

Sammad

Luo

et al. 2022

Biology

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Previous studies reported the physical, transcriptome, and metabolome changes in in vitro acute heat-stressed (38 °C versus 43 °C for 2 h) bovine granulosa cells. Granulosa cells exhibited transient proliferation senescence, oxidative stress, an increased rate of apoptosis, and a decline in steroidogenic activity. In this study, we performed a joint integration and network analysis of metabolomic and transcriptomic data to further narrow down and elucidate the role of differentially expressed genes, important metabolites, and relevant cellular and metabolic pathways in acute heat-stressed granulosa cells. Among the significant (raw p-value < 0.05) metabolic pathways where metabolites and genes converged, this study found vitamin B6 metabolism, glycine, serine and threonine metabolism, phenylalanine metabolism, arginine biosynthesis, tryptophan metabolism, arginine and proline metabolism, histidine metabolism, and glyoxylate and dicarboxylate metabolism. Important significant convergent biological pathways included ABC transporters and protein digestion and absorption, while functional signaling pathways included cAMP, mTOR, and AMPK signaling pathways together with the ovarian steroidogenesis pathway. Among the cancer pathways, the most important pathway was the central carbon metabolism in cancer. Through multiple analysis queries, progesterone, serotonin, citric acid, pyridoxal, L-lysine, succinic acid, L-glutamine, L-leucine, L-threonine, L-tyrosine, vitamin B6, choline, and CYP1B1, MAOB, VEGFA, WNT11, AOX1, ADCY2, ICAM1, PYGM, SLC2A4, SLC16A3, HSD11B2, and NOS2 appeared to be important enriched metabolites and genes, respectively. These genes, metabolites, and metabolic, cellular, and cell signaling pathways comprehensively elucidate the mechanisms underlying the intricate fight between death and survival in acute heat-stressed bovine granulosa cells and essentially help further our understanding (and will help the future quest) of research in this direction.

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“…Additionally, apoptosis can be triggered by a variety of stimuli including inflammatory cytokines and ROS. ROS has been extensively implicated in T cell hyporesponsiveness, apoptosis, and activation [ 24 , 25 ]. To validate this hypothesis, the levels of ROS and SOD were measured to assess the degree of oxidative stress in the spleen of PICS mice.…”

Section: Discussionmentioning

confidence: 99%

Alpinetin Attenuates Persistent Inflammation, Immune Suppression, and Catabolism Syndrome in a Septic Mouse Model

Liu

Wang

Feng

et al. 2021

Journal of Immunology Research

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Patients who survive the acute phase of sepsis can progress to persistent inflammation, immunosuppression, and catabolism syndrome (PICS), which usually results in extended recovery periods and multiple complications. Alpinetin is a flavonoid isolated from Alpinia katsumadai Hayata that has been demonstrated to have anti-inflammatory, antibacterial, and antioxidant activities. The aim of this study was to investigate whether the administration of alpinetin could attenuate PICS in a septic mouse model. Mice were randomly divided into four groups: the (1) sham-operated group, (2) sham+alpinetin (1 mg/kg intravenously infused for once per day after sham operation), (3) cecal ligation and puncture (CLP), and (4) CLP+alpinetin (50 mg/kg intravenously infused for once per day after CLP). Eight days after sham operation or CLP surgery, mice were euthanized for subsequent examination. Alpinetin significantly improved the survival of septic mice. Also, it attenuated the CLP-induced persistent inflammation, immunosuppression, and catabolism syndrome. The level of plasma proinflammatory cytokines and apoptosis of T lymphocytes were obviously decreased by alpinetin as well. Moreover, oxidative stress in the organs was compelling lower in the alpinetin-treated CLP mice. In this clinically relevant model of sepsis, alpinetin ameliorates CLP-induced organ dysfunction and improves the likelihood of survival, possibly through suppressing the inflammatory response, oxidative stress, and apoptosis. These findings suggested that alpinetin could be a potential novel therapeutic approach to prevent sepsis-induced PICS.

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Mitochondria, Oxidative Stress, cAMP Signalling and Apoptosis: A Crossroads in Lymphocytes of Multiple Sclerosis, a Possible Role of Nutraceutics

Cited by 29 publications

References 191 publications

Neuroimmune Crosstalk Between the Peripheral and the Central Immune System in Amyotrophic Lateral Sclerosis

Neuroimmune Crosstalk Between the Peripheral and the Central Immune System in Amyotrophic Lateral Sclerosis

Joint Transcriptome and Metabolome Analysis Prevails the Biological Mechanisms Underlying the Pro-Survival Fight in In Vitro Heat-Stressed Granulosa Cells

Alpinetin Attenuates Persistent Inflammation, Immune Suppression, and Catabolism Syndrome in a Septic Mouse Model

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