Nociceptin/orphanin FQ opioid receptor (NOP) selective ligand MCOPPB links anxiolytic and senolytic effects

Raffaele, Marco; Kovacovicova, Kristina; Biagini, Tommaso; Re, Oriana Lo; Fröhlich, Jan; Giallongo, Sebastiano; Nhan, James D.; Giannone, Antonino Giulio; Cabibi, Daniela; Ivanov, Martin; Tonchev, Anton B.; Mistrík, Martin; Lacey, Matthew J.; Džubák, Petr; Gurská, Soňa; Hajdúch, Marián; Bártek, Jiří; Mazza, Tommaso; Micale, Vincenzo; Curran, Sean P.; Vinciguerra, Manlio

doi:10.1007/s11357-021-00487-y

Cited by 13 publications

(13 citation statements)

References 107 publications

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“…Exploratory activity was evaluated, as previously described with slight modifications [ 38 , 39 , 40 , 41 , 42 , 43 , 44 ]. The apparatus consisted of a cubic metal box (60 × 60 × 60 cm) that was moderately illuminated (80 lux).…”

Section: Methodsmentioning

confidence: 99%

Early Blockade of CB1 Receptors Ameliorates Schizophrenia-like Alterations in the Neurodevelopmental MAM Model of Schizophrenia

et al. 2022

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In agreement with the neurodevelopmental hypothesis of schizophrenia, prenatal exposure of Sprague-Dawley rats to the antimitotic agent methylazoxymethanol acetate (MAM) at gestational day 17 produces long-lasting behavioral alterations such as social withdrawal and cognitive impairment in adulthood, mimicking a schizophrenia-like phenotype. These abnormalities were preceded at neonatal age both by the delayed appearance of neonatal reflexes, an index of impaired brain maturation, and by higher 2-arachidonoylglycerol (2-AG) brain levels. Schizophrenia-like deficits were reversed by early treatment [from postnatal day (PND) 2 to PND 8] with the CB1 antagonist/inverse agonist AM251 (0.5 mg/kg/day). By contrast, early CB1 blockade affected the behavioral performance of control rats which was paralleled by enhanced 2-AG content in the prefrontal cortex (PFC). These results suggest that prenatal MAM insult leads to premorbid anomalies at neonatal age via altered tone of the endocannabinoid system, which may be considered as an early marker preceding the development of schizophrenia-like alterations in adulthood.

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Section: Methodsmentioning

confidence: 99%

Early Blockade of CB1 Receptors Ameliorates Schizophrenia-like Alterations in the Neurodevelopmental MAM Model of Schizophrenia

et al. 2022

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“…A great help was given by the application of the high throughput automatized screening (HTS) technology, which recently led to discover new senolytic drug families, demonstrating to be a reliable tool. This approach allows testing thousands of existing molecules, available in the market as chemical libraries, to be repurposed in in vitro senescence models [ 4 ].…”

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confidence: 99%

“…In our recent report published on Geroscience [ 4 ], we tested through HTS the LOPAC®Pfizer library compounds on a human fibroblast aphidicolin-induced senescence model, identifying the [1-(1-Methylcyclooctyl)-4-piperidinyl]-2-[(3R)-3-piperidinyl]-1H-benzimidazole (MCOPPB), a nociceptin opiod receptor (NOP) agonist and a pre-clinically tested anxiolytic, as a new potent senolytic. We found that MCOPPB was effective in killing senescence cells also when the process was induced by a chemotherapeutic drug (Doxorubicin) in HCC cells.…”

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confidence: 99%

“…In adult mice, MCOPPB significantly reduced locomotion – as expected with the administration of anxiolytic, and reduced also the senescence cell burden in peripheral tissues – in the white adipose tissue as well as in liver. The senescence cell clarence was accompanied by mild liver stress, characterized by a low grade of steatosis, and by an increase in adipocytes diameter together with an increased trend in body weight gain [ 4 ]. We hypothesize that these accompanying effects could be largely attributed to the decreased locomotion observed in the mice after MCOPPB administration.…”

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confidence: 99%

“…Pharmacogenetic and pharmacologic (using D + Q) clearance of senescent cells alleviated obesity-related anxiety and NAFLD in mice [ 7 ]. Altogether, these data lead us to speculate that the anxiolytic and senolytic effects of MCOPPB might be connected [ 4 ]. It is unclear whether senescent cells can induce anxiety-like behavior via systemic SASP-dependent effects or, vice versa through the immune system / neurotransmitters functioning.…”

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confidence: 99%

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Targeting anxiety and senescence with senolytics

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Nrf2 driven macrophage responses in diverse pathophysiological contexts: Disparate pieces from a shared molecular puzzle

Ganesh

Ganesan

et al. 2022

BioFactors

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The wide anatomical distribution of macrophages and their vast array of functions match various polarization states and their involvement in homeostasis and disease. The confluence of different cellular signaling networks, including direct involvement in inflammation, at the doorstep of the transcription factor Nuclear Factor‐ erythroid (NF‐E2) p45‐related factor 2 (Nrf2) activation raises the importance of deciphering the molecular circuitry at the background of multiple‐discrete and antagonistic yet flexible and contextual pathways. While we primarily focus on wound healing and repair mechanisms that are affected in diabetic foot ulcers (DFUs), we strive to explore the striking similarities and differences in molecular events including inflammation, angiogenesis, and fibrosis during tissue injury and wound persistence that accumulates pro‐inflammatory senescent macrophages, as a means to identify possible targets or cellular mediators to lessen DFU disease burden. In addition, the role of iron in the modulation of Nrf2 response in macrophages is crucial and reviewed here. Targeted approaches, unlike conventional treatments, in DFU management will require the review and re‐assessment of mediators with relevance to other pathological conditions.

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Nociceptin/orphanin FQ opioid receptor (NOP) selective ligand MCOPPB links anxiolytic and senolytic effects

Cited by 13 publications

References 107 publications

Early Blockade of CB1 Receptors Ameliorates Schizophrenia-like Alterations in the Neurodevelopmental MAM Model of Schizophrenia

Early Blockade of CB1 Receptors Ameliorates Schizophrenia-like Alterations in the Neurodevelopmental MAM Model of Schizophrenia

Targeting anxiety and senescence with senolytics

Nrf2 driven macrophage responses in diverse pathophysiological contexts: Disparate pieces from a shared molecular puzzle

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