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.

Základní údaje

Originální název

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

Autoři

RAFFAELE, M., K. KOVACOVICOVA, T. BIAGINI, O. LO RE, J. FROHLICH, Sebastiano GIALLONGO (380 Itálie, domácí), J. D. NHAN, A. G. GIANNONE, D. CABIBI, M. IVANOV, A. B. TONCHEV, Martin MISTRIK (203 Česká republika), M. LACEY, Petr DZUBAK (203 Česká republika), Sona GURSKA (203 Česká republika), Marian HAJDUCH (203 Česká republika), Jiri BARTEK (203 Česká republika), T. MAZZA, V. MICALE, S. P. CURRAN a M. VINCIGUERRA (garant)

Vydání

GEROSCIENCE, DORDRECHT, SPRINGER, 2022, 2509-2715

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30227 Geriatrics and gerontology

Stát vydavatele

Nizozemské království

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 5.600

Kód RIV

RIV/00216224:14110/22:00125369

Organizační jednotka

Lékařská fakulta

DOI

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

UT WoS

000722174500001

Klíčová slova anglicky

Senolytic; NOP; Senescence; Aging

Štítky

14110513, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 15. 2. 2022 10:15, Mgr. Tereza Miškechová

Anotace

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.

Návaznosti

LM2018130, projekt VaV

Název: Národní infrastruktura chemické biologie (Akronym: CZ-OPENSCREEN)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, CZ-OPENSCREEN: National Infrastructure for Chemical Biology

LM2018133, projekt VaV

Název: Český národní uzel Evropské infrastruktury pro translační medicínu (Akronym: EATRIS-ERIC-CZ)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Involvement of Czech Translational Medicine Infrastructure to the European Advanced Translational Research Infrastructure in Medicine

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 a M. VINCIGUERRA. Nociceptin/orphanin FQ opioid receptor (NOP) selective ligand MCOPPB links anxiolytic and senolytic effects. GEROSCIENCE. DORDRECHT: SPRINGER, 2022, roč. 44, č. 1, s. 463-483. ISSN 2509-2715. Dostupné z: 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 a M. VINCIGUERRA. Nociceptin/orphanin FQ opioid receptor (NOP) selective ligand MCOPPB links anxiolytic and senolytic effects. \textit{GEROSCIENCE}. DORDRECHT: SPRINGER, 2022, roč.~44, č.~1, s.~463-483. ISSN~2509-2715. Dostupné z: https://dx.doi.org/10.1007/s11357-021-00487-y.

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