The Signaling Pathway of the ADP Receptor P2Y12 in the Immune System: Recent Discoveries and New Challenges

被引：18

作者：

Entsie, Philomena ^{[1
]}

Kang, Ying ^{[1
]}

Amoafo, Emmanuel Boadi ^{[1
]}

Schoeneberg, Torsten ^{[2
]}

Liverani, Elisabetta ^{[1
]}

机构：

[1] North Dakota State Univ, Coll Hlth Profess, Sch Pharm, Dept Pharmaceut Sci, Fargo, ND 58105 USA

[2] Univ Leipzig, Rudolf Schonheimer Inst Biochem, Med Fac, Div Mol Biochem, D-04103 Leipzig, Germany

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2023年 / 24卷 / 07期

关键词：

P2Y(12) signaling pathway; immune system; antiplatelet therapy; SMOOTH-MUSCLE-CELLS; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; ELEVATION MYOCARDIAL-INFARCTION; ACUTE CORONARY SYNDROME; P2Y12; RECEPTORS; PLATELET ACTIVATION; ACTIVE METABOLITES; ESTROGEN-RECEPTOR; LIPID RAFTS; P-SELECTIN;

D O I：

10.3390/ijms24076709

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

P2Y(12) is a G-protein-coupled receptor that is activated upon ADP binding. Considering its well-established role in platelet activation, blocking P2Y(12) has been used as a therapeutic strategy for antiplatelet aggregation in cardiovascular disease patients. However, receptor studies have shown that P2Y(12) is functionally expressed not only in platelets and the microglia but also in other cells of the immune system, such as in monocytes, dendritic cells, and T lymphocytes. As a result, studies were carried out investigating whether therapies targeting P2Y(12) could also ameliorate inflammatory conditions, such as sepsis, rheumatoid arthritis, neuroinflammation, cancer, COVID-19, atherosclerosis, and diabetes-associated inflammation in animal models and human subjects. This review reports what is known about the expression of P2Y(12) in the cells of the immune system and the effect of P2Y(12) activation and/or inhibition in inflammatory conditions. Lastly, we will discuss the major problems and challenges in studying this receptor and provide insights on how they can be overcome.

引用

页数：23

共 172 条

[1]

Abadjian MCZ, 2017, ADV EXP MED BIOL, V1036, P229, DOI [10.1007/978-3-319-67577-0_15, 10.1097/PPO.0000000000000118]

[2] P2Y12 Inhibitors versus Aspirin Monotherapy for Long-term Secondary Prevention of Atherosclerotic Cardiovascular Disease Events: A Systematic Review and Meta-analysis [J].

Al-Abdouh, Ahmad ;

Abusnina, Waiel ;

Mhanna, Mohammed ;

Radideh, Qais ;

Alzu'bi, Hossam ;

Abu Rmilah, Anan ;

Jabri, Ahmad ;

Barbarawi, Mahmoud ;

Obeidat, Khaldun ;

Alabduh, Taqwa ;

Michos, Erin D. ;

Alnabelsi, Talal ;

Paul, Timir K. .

CURRENT PROBLEMS IN CARDIOLOGY, 2022, 47 (10)

[3] P2Y12 antagonism results in altered interactions between platelets and regulatory T cells during sepsis [J].

Albayati, Samara ;

Vemulapalli, Harika ;

Tsygankov, Alexander Y. ;

Liverani, Elisabetta .

JOURNAL OF LEUKOCYTE BIOLOGY, 2021, 110 (01) :141-153

[4] Differential Expression of the Metabotropic P2Y Receptor Family in the Cortex Following Status Epilepticus and Neuroprotection via P2Y1 Antagonism in Mice [J].

Alves, Mariana ;

Smith, Jonathon ;

Engel, Tobias .

FRONTIERS IN PHARMACOLOGY, 2020, 10

[5]

Amsterdam EA, 2014, J AM COLL CARDIOL, V64, P2713, DOI [10.1016/j.jacc.2014.09.017, 10.1016/j.jacc.2014.10.011, 10.1161/CIR.0000000000000134, 10.1016/j.jacc.2014.09.016]

[6]

Anderson NM, 2020, CURR BIOL, V30, pR921, DOI 10.1016/j.cub.2020.06.081

[7] International Expert Consensus on Switching Platelet P2Y12 Receptor-Inhibiting Therapies [J].