Serotonergic drug repurposing in multiple sclerosis: A new possibility for disease-modifying therapy

Melnikov, Mikhail; Kasatkin, D. S.; Lopatina, Anna; Спирин, Н Н; Boyко, Alexey; Pashenkov, Мikhail

doi:10.3389/fneur.2022.920408

Cited by 6 publications

(3 citation statements)

References 42 publications

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“…It is probably, that antidepressants could be tested as an additional treatment to the first-line DMT of MS ( 71 – 74 ). In particular, according to our recent retrospective pilot study, the addition of therapy with fluoxetine in patients with relapsing-remitting MS with a suboptimal response to the first-line DMT (IFN-β or glatiramer acetate) can reduce the disease activity, preventing the switching to the more aggressive second-line DMT ( 75 ). Although this is preliminary data, which needs to be confirmed in prospective studies with a control group, the results of this analysis are in line with the data of other studies and suggest the potential clinical efficacy of antidepressants as a pathogenetic treatment of MS ( 20 ).…”

Section: Discussionmentioning

confidence: 99%

Th17-cells in depression: Implication in multiple sclerosis

Melnikov

Lopatina

2022

Front. Immunol.

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Depression is one of the most common neuropsychological symptoms of multiple sclerosis. However, in addition to mood disorder, depression can also influence on multiple sclerosis course. The mechanism of this dependence is not fully understood. The recent studies suggest the possible common immune mechanisms in the pathogenesis of depression and multiple sclerosis. In particular, it was shown that along with biogenic amines disturbance, neuroinflammation also play an important role in the pathogenesis of depression. Significant attention is drawn to Th17-cells subsets, which are considered as critical players in the pathogenesis of inflammatory diseases of the central nervous system, including multiple sclerosis. This brief report reviews the literature data on the role of neuroinflammation in the reciprocal influence of multiple sclerosis and depression with focus on Th17-cells, which may underlie pathogenetic mechanisms of both this diseases.

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Section: Discussionmentioning

confidence: 99%

Th17-cells in depression: Implication in multiple sclerosis

Melnikov

Lopatina

2022

Front. Immunol.

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“…Low levels of 5-HT are found in MS patients. Serotoninergic modulators such as SSRIs activate microglia and decrease oxidative stress and neuroinflammation [200,201]. N-acetyl-5-methoxytrypatmine (melatonin), another tryptamine derivative, acts as a signaling molecule at the CNS level and regulates immune response, oxidative stress, and apoptosis.…”

Section: Multiple Sclerosismentioning

confidence: 99%

Gut Bacteria Provide Genetic and Molecular Reporter Systems to Identify Specific Diseases

Dicks

2024

IJMS

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With genetic information gained from next-generation sequencing (NGS) and genome-wide association studies (GWAS), it is now possible to select for genes that encode reporter molecules that may be used to detect abnormalities such as alcohol-related liver disease (ARLD), cancer, cognitive impairment, multiple sclerosis (MS), diabesity, and ischemic stroke (IS). This, however, requires a thorough understanding of the gut–brain axis (GBA), the effect diets have on the selection of gut microbiota, conditions that influence the expression of microbial genes, and human physiology. Bacterial metabolites such as short-chain fatty acids (SCFAs) play a major role in gut homeostasis, maintain intestinal epithelial cells (IECs), and regulate the immune system, neurological, and endocrine functions. Changes in butyrate levels may serve as an early warning of colon cancer. Other cancer-reporting molecules are colibactin, a genotoxin produced by polyketide synthetase-positive Escherichia coli strains, and spermine oxidase (SMO). Increased butyrate levels are also associated with inflammation and impaired cognition. Dysbiosis may lead to increased production of oxidized low-density lipoproteins (OX-LDLs), known to restrict blood vessels and cause hypertension. Sudden changes in SCFA levels may also serve as a warning of IS. Early signs of ARLD may be detected by an increase in regenerating islet-derived 3 gamma (REG3G), which is associated with changes in the secretion of mucin-2 (Muc2). Pro-inflammatory molecules such as cytokines, interferons, and TNF may serve as early reporters of MS. Other examples of microbial enzymes and metabolites that may be used as reporters in the early detection of life-threatening diseases are reviewed.

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“…Currently, serotoninergic modulators such as SSRIs are a viable treatment option [159]. These modulators have additional effects on microglial activation and decrease oxidative stress and neuroinflammation [160].…”

Section: Modulation Of Redox Signaling and Inflammation By Gut Microb...mentioning

confidence: 99%

The Gut–Brain Axis as a Therapeutic Target in Multiple Sclerosis

Buga

Pădureanu

Riza

et al. 2023

Cells

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The CNS is very susceptible to oxidative stress; the gut microbiota plays an important role as a trigger of oxidative damage that promotes mitochondrial dysfunction, neuroinflammation, and neurodegeneration. In the current review, we discuss recent findings on oxidative-stress-related inflammation mediated by the gut–brain axis in multiple sclerosis (MS). Growing evidence suggests targeting gut microbiota can be a promising strategy for MS management. Intricate interaction between multiple factors leads to increased intra- and inter-individual heterogeneity, frequently painting a different picture in vivo from that obtained under controlled conditions. Following an evidence-based approach, all proposed interventions should be validated in clinical trials with cohorts large enough to reach significance. Our review summarizes existing clinical trials focused on identifying suitable interventions, the suitable combinations, and appropriate timings to target microbiota-related oxidative stress. Most studies assessed relapsing–remitting MS (RRMS); only a few studies with very limited cohorts were carried out in other MS stages (e.g., secondary progressive MS–SPMS). Future trials must consider an extended time frame, perhaps starting with the perinatal period and lasting until the young adult period, aiming to capture as many complex intersystem interactions as possible.

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Serotonergic drug repurposing in multiple sclerosis: A new possibility for disease-modifying therapy

Cited by 6 publications

References 42 publications

Th17-cells in depression: Implication in multiple sclerosis

Th17-cells in depression: Implication in multiple sclerosis

Gut Bacteria Provide Genetic and Molecular Reporter Systems to Identify Specific Diseases

The Gut–Brain Axis as a Therapeutic Target in Multiple Sclerosis

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