Orexins as Novel Therapeutic Targets in Inflammatory and Neurodegenerative Diseases

Couvineau, Alain; Voisin, Thierry; Nicole, Pascal; Gratio, Valérie; Abad, Catalina; Tan, Yossan‐Var

doi:10.3389/fendo.2019.00709

Cited by 57 publications

(62 citation statements)

References 155 publications

(200 reference statements)

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“…anti-in ammatory) properties. Studies show that orexins may have therapeutic potential in several pathologies with a single immune component, including multiple sclerosis, Alzheimer's disease, obesity, septic shock, and cancer [41]. We suggest more investigations into dietary-dependent neuropathy in MS patients and more in-depth examinations of the role of BMI in MS patients.…”

Section: Discussionmentioning

confidence: 91%

The Relationship Between Serum Orexin A, TGF-β, and Leptin Levels with Body Mass Index in Multiple Sclerosis Patients

Moharami

Nourazarian

Nikanfar

et al. 2021

Preprint

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Backgrounds: Multiple Sclerosis (MS) is a chronic inflammatory and autoimmune disease linked to several inflammatory and dietary parameters. This study was carried out to determine the relationship between serum leptin, orexin-A, and TGF-β levels with BMI in MS patients.Methods and results: In this cross-sectional study, 25 relapsing-remitting multiple sclerosis (RRMS) patients and 40 healthy controls were enrolled. The serum level of Leptin, Orexin-A, and TGF- were measured by the Enzyme-linked immunosorbent assay (ELISA). The data was analyzed using descriptive statistics, t-test, Chi-square test, and Linear regression test. A total of 65 volunteers, including 25 MS patients and 40 healthy, were enrolled in the study. The mean age of individuals in the case and control groups was 38.04 ± 7.53 and 40.23 ± 5.88. There were no statistically significant differences between the case and control groups regarding gender, age, alcohol, and cigarette use (P>0.05). The mean serum levels of Orexin-A and TGF-ß were lower among multiple sclerosis patients than in healthy controls, but leptin was higher (42.8 vs. 18.9 ng/ml, P<0.001). The relationship between BMI and serum levels of Orexin-A, TGF-ß, and Leptin among Multiple Sclerosis patients was not statistically significant (P > 0.05).Conclusion: Our results showed that the serum levels of Orexin-A and TGF-β were significantly lower. The serum level of leptin was higher among multiple sclerosis patients than among healthy controls. Also, there was no statistically significant relationship between BMI and serum levels of Orexin-A, TGF-ß, and Leptin among multiple sclerosis patients.

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Section: Discussionmentioning

confidence: 91%

The Relationship Between Serum Orexin A, TGF-β, and Leptin Levels with Body Mass Index in Multiple Sclerosis Patients

Moharami

Nourazarian

Nikanfar

et al. 2021

Preprint

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“…As a general remark, the effect of OXB has been less investigated, possibly due to its considerably lesser affinity for OX2. However, Sokołowska et al [ 43 ] demonstrated a potent antioxidant effect of OXB in primary neuronal rat culture and a therapeutic use has also been hypothesized [ 44 ]. It should be noted that our findings are of particular interest, since redox status regulation generally plays a central role in follicular function.…”

Section: Discussionmentioning

confidence: 99%

Effects of Orexin B on Swine Granulosa and Endothelial Cells

Grasselli

Bussolati

Grolli

et al. 2021

Animals

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In addition to the well-known central modulatory role of orexins, we recently demonstrated a peripheral involvement in swine granulosa cells for orexin A and in adipose tissue for orexin B (OXB). The aim of present research was to verify immunolocalization of OXB and its potential role in modulating the main features of swine granulosa cells. In particular, we explored the effects on granulosa cell proliferation (through the incorporation of bromodeoxyuridine), cell metabolic activity (as indirect evaluation by the assessment of ATP), steroidogenic activity (by immunoenzymatic examination) and redox status (evaluating the production of superoxide anion by means of the WST test, production of nitric oxide through the use of the Griess test and the non-enzymatic reducing power by FRAP test). Our data point out that OXB does not modify granulosa cell growth, steroidogenesis and superoxide anion generation. On the contrary, the peptide stimulates (p < 0.05) nitric oxide output and non-enzymatic reducing power. Since new vessel growth is crucial for ovarian follicle development, a further aim of this study was to explore the expression of prepro-orexin and the effects of OXB on swine aortic endothelial cells. We found that the peptide is ineffective in modulating cell growth, while it inhibits redox status parameters. In addition, we demonstrated a stimulatory effect on angiogenesis evaluated in fibrin gel angiogenesis assay. Taken together, OXB appears to be potentially involved in the modulation of redox status in granulosa and endothelial cells and we could argue an involvement of the peptide in the follicular angiogenic events.

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“…Thus, OXA has an immunoregulatory and neuroprotective action, inhibiting apoptosis and reducing inflammation. Moreover, OXA seems to have an action on microglia, with promising implications not only for tumors and inflammatory diseases but also for neurodegenerative diseases, although data on these are still scarce [ 157 ]. The orexin receptor antagonist suvorexant might be useful for the prevention and treatment of AD because of its neuroprotective effect, with reduction of β-amyloid plaques and improvement of synaptic plasticity [ 158 ].…”

Section: Orexin Cancer and Neurodegenerative Diseasesmentioning

confidence: 99%

Focus on the Complex Interconnection between Cancer, Narcolepsy and Other Neurodegenerative Diseases: A Possible Case of Orexin-Dependent Inverse Comorbidity

Mogavero

Silvani

DelRosso

et al. 2021

Cancers

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Conditions such as Alzheimer’s (AD) and Parkinson’s diseases (PD) are less prevalent in cancer survivors and, overall, cancer is less prevalent in subjects with these neurodegenerative disorders. This seems to suggest that a propensity towards one type of disease may decrease the risk of the other. In addition to epidemiologic data, there is also evidence of a complex biological interconnection, with genes, proteins, and pathways often showing opposite dysregulation in cancer and neurodegenerative diseases. In this narrative review, we focus on the possible role played by orexin signaling, which is altered in patients with narcolepsy type 1 and in those with AD and PD, and which has been linked to β-amyloid brain levels and inflammation in mouse models and to cancer in cell lines. Taken together, these lines of evidence depict a possible case of inverse comorbidity between cancer and neurodegenerative disorders, with a role played by orexins. These considerations suggest a therapeutic potential of orexin modulation in diverse pathologies such as narcolepsy, neurodegenerative disorders, and cancer.

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Orexins as Novel Therapeutic Targets in Inflammatory and Neurodegenerative Diseases

Cited by 57 publications

References 155 publications

The Relationship Between Serum Orexin A, TGF-β, and Leptin Levels with Body Mass Index in Multiple Sclerosis Patients

The Relationship Between Serum Orexin A, TGF-β, and Leptin Levels with Body Mass Index in Multiple Sclerosis Patients

Effects of Orexin B on Swine Granulosa and Endothelial Cells

Focus on the Complex Interconnection between Cancer, Narcolepsy and Other Neurodegenerative Diseases: A Possible Case of Orexin-Dependent Inverse Comorbidity

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