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

J 2022

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

RAFFAELE, M., K. KOVACOVICOVA, T. BIAGINI, O. LO RE, J. FROHLICH et. al.

Basic information

Original name

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

Authors

RAFFAELE, M., K. KOVACOVICOVA, T. BIAGINI, O. LO RE, J. FROHLICH, Sebastiano GIALLONGO (380 Italy, belonging to the institution), J. D. NHAN, A. G. GIANNONE, D. CABIBI, M. IVANOV, A. B. TONCHEV, Martin MISTRIK (203 Czech Republic), M. LACEY, Petr DZUBAK (203 Czech Republic), Sona GURSKA (203 Czech Republic), Marian HAJDUCH (203 Czech Republic), Jiri BARTEK (203 Czech Republic), T. MAZZA, V. MICALE, S. P. CURRAN and M. VINCIGUERRA (guarantor)

Edition

GEROSCIENCE, DORDRECHT, SPRINGER, 2022, 2509-2715

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30227 Geriatrics and gerontology

Country of publisher

Netherlands

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 5.600

RIV identification code

RIV/00216224:14110/22:00125369

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1007/s11357-021-00487-y

UT WoS

000722174500001

Keywords in English

Senolytic; NOP; Senescence; Aging

Abstract

V originále

Accumulation of senescent cells may drive age-associated alterations and pathologies. Senolytics are promising therapeutics that can preferentially eliminate senescent cells. Here, we performed a high-throughput automatized screening (HTS) of the commercial LOPAC (R) Pfizer library on aphidicolin-induced senescent human fibroblasts, to identify novel senolytics. We discovered the nociceptin receptor FQ opioid receptor (NOP) selective ligand 1-[1-(1-methylcyclooctyl)-4-piperidinyl]-2-[(3R)-3-piperidinyl]-1H-benzimidazole (MCOPPB, a compound previously studied as potential anxiolytic) as the best scoring hit. The ability of MCOPPB to eliminate senescent cells in in vitro models was further tested in mice and in C. elegans. MCOPPB reduced the senescence cell burden in peripheral tissues but not in the central nervous system. Mice and worms exposed to MCOPPB also exhibited locomotion and lipid storage changes. Mechanistically, MCOPPB treatment activated transcriptional networks involved in the immune responses to external stressors, implicating Toll-like receptors (TLRs). Our study uncovers MCOPPB as a NOP ligand that, apart from anxiolytic effects, also shows tissue-specific senolytic effects.

Links

LM2018130, research and development project

Name: Národní infrastruktura chemické biologie (Acronym: CZ-OPENSCREEN)

Investor: Ministry of Education, Youth and Sports of the CR

LM2018133, research and development project

Name: Český národní uzel Evropské infrastruktury pro translační medicínu (Acronym: EATRIS-ERIC-CZ)

Investor: Ministry of Education, Youth and Sports of the CR

Citovat

RAFFAELE, M., K. KOVACOVICOVA, T. BIAGINI, O. LO RE, J. FROHLICH, Sebastiano GIALLONGO, J. D. NHAN, A. G. GIANNONE, D. CABIBI, M. IVANOV, A. B. TONCHEV, Martin MISTRIK, M. LACEY, Petr DZUBAK, Sona GURSKA, Marian HAJDUCH, Jiri BARTEK, T. MAZZA, V. MICALE, S. P. CURRAN and M. VINCIGUERRA. Nociceptin/orphanin FQ opioid receptor (NOP) selective ligand MCOPPB links anxiolytic and senolytic effects. GEROSCIENCE. DORDRECHT: SPRINGER, 2022, vol. 44, No 1, p. 463-483. ISSN 2509-2715. Available from: https://dx.doi.org/10.1007/s11357-021-00487-y.

@article{1834317,
   author = {Raffaele, M. and Kovacovicova, K. and Biagini, T. and Lo Re, O. and Frohlich, J. and Giallongo, Sebastiano and Nhan, J. D. and Giannone, A. G. and Cabibi, D. and Ivanov, M. and Tonchev, A. B. and Mistrik, Martin and Lacey, M. and Dzubak, Petr and Gurska, Sona and Hajduch, Marian and Bartek, Jiri and Mazza, T. and Micale, V. and Curran, S. P. and Vinciguerra, M.},
   article_location = {DORDRECHT},
   article_number = {1},
   doi = {http://dx.doi.org/10.1007/s11357-021-00487-y},
   keywords = {Senolytic; NOP; Senescence; Aging},
   language = {eng},
   issn = {2509-2715},
   journal = {GEROSCIENCE},
   title = {Nociceptin/orphanin FQ opioid receptor (NOP) selective ligand MCOPPB links anxiolytic and senolytic effects},
   url = {https://link.springer.com/article/10.1007/s11357-021-00487-y},
   volume = {44},
   year = {2022}
}

TY  - JOUR
ID  - 1834317
AU  - Raffaele, M. - Kovacovicova, K. - Biagini, T. - Lo Re, O. - Frohlich, J. - Giallongo, Sebastiano - Nhan, J. D. - Giannone, A. G. - Cabibi, D. - Ivanov, M. - Tonchev, A. B. - Mistrik, Martin - Lacey, M. - Dzubak, Petr - Gurska, Sona - Hajduch, Marian - Bartek, Jiri - Mazza, T. - Micale, V. - Curran, S. P. - Vinciguerra, M.
PY  - 2022
TI  - Nociceptin/orphanin FQ opioid receptor (NOP) selective ligand MCOPPB links anxiolytic and senolytic effects
JF  - GEROSCIENCE
VL  - 44
IS  - 1
SP  - 463-483
EP  - 463-483
PB  - SPRINGER
SN  - 25092715
KW  - Senolytic
KW  - NOP
KW  - Senescence
KW  - Aging
UR  - https://link.springer.com/article/10.1007/s11357-021-00487-y
N2  - Accumulation of senescent cells may drive age-associated alterations and pathologies. Senolytics are promising therapeutics that can preferentially eliminate senescent cells. Here, we performed a high-throughput automatized screening (HTS) of the commercial LOPAC (R) Pfizer library on aphidicolin-induced senescent human fibroblasts, to identify novel senolytics. We discovered the nociceptin receptor FQ opioid receptor (NOP) selective ligand 1-[1-(1-methylcyclooctyl)-4-piperidinyl]-2-[(3R)-3-piperidinyl]-1H-benzimidazole (MCOPPB, a compound previously studied as potential anxiolytic) as the best scoring hit. The ability of MCOPPB to eliminate senescent cells in in vitro models was further tested in mice and in C. elegans. MCOPPB reduced the senescence cell burden in peripheral tissues but not in the central nervous system. Mice and worms exposed to MCOPPB also exhibited locomotion and lipid storage changes. Mechanistically, MCOPPB treatment activated transcriptional networks involved in the immune responses to external stressors, implicating Toll-like receptors (TLRs). Our study uncovers MCOPPB as a NOP ligand that, apart from anxiolytic effects, also shows tissue-specific senolytic effects.
ER  -

RAFFAELE, M., K. KOVACOVICOVA, T. BIAGINI, O. LO RE, J. FROHLICH, Sebastiano GIALLONGO, J. D. NHAN, A. G. GIANNONE, D. CABIBI, M. IVANOV, A. B. TONCHEV, Martin MISTRIK, M. LACEY, Petr DZUBAK, Sona GURSKA, Marian HAJDUCH, Jiri BARTEK, T. MAZZA, V. MICALE, S. P. CURRAN and M. VINCIGUERRA. Nociceptin/orphanin FQ opioid receptor (NOP) selective ligand MCOPPB links anxiolytic and senolytic effects. \textit{GEROSCIENCE}. DORDRECHT: SPRINGER, 2022, vol.~44, No~1, p.~463-483. ISSN~2509-2715. Available from: https://dx.doi.org/10.1007/s11357-021-00487-y.

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