The Relaxin Peptide Family - Potential Future Hope for Neuroprotective Therapy? A Short Review

Overview

Journal Neural Regen Res

Date 2018 Apr 7

PMID 29623915

Citations 3

Authors

Marius Nistor

Martin Schmidt

Rene Schiffner

Affiliations

Soon will be listed here.

Abstract

Since its discovery in the 1920's the relaxin peptide hormone family has not only grown in number to now seven members (relaxin-1, relaxin-2, relaxin-3, insulin-like peptide (INSL) 3, INSL4, INSL5 and INSL6), but ever more effects, suchs as vasodilatory, angiogenic, anti-apoptopic, anti-fibriotic and anti-inflammatory, have been linked to them. While relaxin-2 has mainly been investigated in the context of cardiac protection, most comprehensively in the RELAX-AHF and RELAX AHF2 studies, a small number of studies have furthermore assessed the potential neuroprotective effects of especially relaxin-2 and other members of the relaxin family. In this short review we summarise and discuss recent efforts to utilize relaxin hormones for neuroprotection and point out potential future fields of research and translational applications. While many questions still need to be answered, the promising results of the available studies definitely warrant future well-designed studies on neuroprotection by relaxin peptides.

Citing Articles

Molecular Mechanisms for the Vicious Cycle between Insulin Resistance and the Inflammatory Response in Obesity.

Szukiewicz D Int J Mol Sci. 2023; 24(12).

PMID: 37372966 PMC: 10298329. DOI: 10.3390/ijms24129818.

Myocardial Infarction-Induced INSL6 Decrease Contributes to Breast Cancer Progression.

Zheng Y, Gao W, Wang S, Qi B, Qi Z, Hu X Dis Markers. 2023; 2023:8702914.

PMID: 36798786 PMC: 9928516. DOI: 10.1155/2023/8702914.

The role of peptidase neurolysin in neuroprotection and neural repair after stroke.

Karamyan V Neural Regen Res. 2020; 16(1):21-25.

PMID: 32788443 PMC: 7818881. DOI: 10.4103/1673-5374.284904.

References

Bischoff S, Schmidt M, Lehmann T, Irintchev A, Schubert H, Jung C . Increase of cortical cerebral blood flow and further cerebral microcirculatory effects of Serelaxin in a sheep model. Am J Physiol Heart Circ Physiol. 2016; 311(3):H613-20. DOI: 10.1152/ajpheart.00118.2016. View

Conrad K, Shroff S . Effects of relaxin on arterial dilation, remodeling, and mechanical properties. Curr Hypertens Rep. 2011; 13(6):409-20. DOI: 10.1007/s11906-011-0231-x. View

Wilson B, Connell B, Saleh T . Relaxin-induced reduction of infarct size in male rats receiving MCAO is dependent on nitric oxide synthesis and not estrogenic mechanisms. Neurosci Lett. 2005; 393(2-3):160-4. DOI: 10.1016/j.neulet.2005.09.059. View

Ma L, Gul R, Habibi J, Yang M, Pulakat L, Whaley-Connell A . Nebivolol improves diastolic dysfunction and myocardial remodeling through reductions in oxidative stress in the transgenic (mRen2) rat. Am J Physiol Heart Circ Physiol. 2012; 302(11):H2341-51. PMC: 3378296. DOI: 10.1152/ajpheart.01126.2011. View

Milia P, Caserio M, Bani D, Rastelli T, Sonaglia F, Bigazzi B . Efficacy of relaxin on functional recovery of post stroke patients. Ital J Anat Embryol. 2014; 118(1 Suppl):92-7. View

Nistor M, Behringer W, Schmidt M, Schiffner R . A Systematic Review of Neuroprotective Strategies during Hypovolemia and Hemorrhagic Shock. Int J Mol Sci. 2017; 18(11). PMC: 5713217. DOI: 10.3390/ijms18112247. View

Rickards C . Cerebral Blood-Flow Regulation During Hemorrhage. Compr Physiol. 2015; 5(4):1585-621. DOI: 10.1002/cphy.c140058. View

Wilkinson T, Speed T, Tregear G, Bathgate R . Evolution of the relaxin-like peptide family. BMC Evol Biol. 2005; 5:14. PMC: 551602. DOI: 10.1186/1471-2148-5-14. View

Chan S, Sweet J, Cipolla M . Treatment for cerebral small vessel disease: effect of relaxin on the function and structure of cerebral parenchymal arterioles during hypertension. FASEB J. 2013; 27(10):3917-27. PMC: 4046185. DOI: 10.1096/fj.13-230797. View

10.

Ghosh R, Banerjee K, Tummala R, Ball S, Ravakhah K, Gupta A . Serelaxin in acute heart failure: Most recent update on clinical and preclinical evidence. Cardiovasc Ther. 2016; 35(1):55-63. DOI: 10.1111/1755-5922.12231. View

11.

Halls M, Bathgate R, Sutton S, Dschietzig T, Summers R . International Union of Basic and Clinical Pharmacology. XCV. Recent advances in the understanding of the pharmacology and biological roles of relaxin family peptide receptors 1-4, the receptors for relaxin family peptides. Pharmacol Rev. 2015; 67(2):389-440. PMC: 4394689. DOI: 10.1124/pr.114.009472. View

12.

Heckbert S, Vedder N, Hoffman W, Winn R, Hudson L, Jurkovich G . Outcome after hemorrhagic shock in trauma patients. J Trauma. 1998; 45(3):545-9. DOI: 10.1097/00005373-199809000-00022. View

13.

Bergeron L, Willcox J, Alibhai F, Connell B, Saleh T, Wilson B . Relaxin peptide hormones are protective during the early stages of ischemic stroke in male rats. Endocrinology. 2014; 156(2):638-46. PMC: 4298330. DOI: 10.1210/en.2014-1676. View

14.

Chan S, Cipolla M . Relaxin causes selective outward remodeling of brain parenchymal arterioles via activation of peroxisome proliferator-activated receptor-γ. FASEB J. 2011; 25(9):3229-39. PMC: 3157692. DOI: 10.1096/fj.10-175471. View

15.

. Top heart-failure contender serelaxin flops. Nat Biotechnol. 2017; 35(4):297. DOI: 10.1038/nbt0417-297b. View

16.

Sarwar M, Du X, Dschietzig T, Summers R . The actions of relaxin on the human cardiovascular system. Br J Pharmacol. 2016; 174(10):933-949. PMC: 5406304. DOI: 10.1111/bph.13523. View

17.

Bathgate R, Halls M, van der Westhuizen E, Callander G, Kocan M, Summers R . Relaxin family peptides and their receptors. Physiol Rev. 2013; 93(1):405-80. DOI: 10.1152/physrev.00001.2012. View

18.

Debrah D, Novak J, Matthews J, Ramirez R, Shroff S, Conrad K . Relaxin is essential for systemic vasodilation and increased global arterial compliance during early pregnancy in conscious rats. Endocrinology. 2006; 147(11):5126-31. DOI: 10.1210/en.2006-0567. View

19.

Ma S, Shen P, Burazin T, Tregear G, Gundlach A . Comparative localization of leucine-rich repeat-containing G-protein-coupled receptor-7 (RXFP1) mRNA and [33P]-relaxin binding sites in rat brain: restricted somatic co-expression a clue to relaxin action?. Neuroscience. 2006; 141(1):329-44. DOI: 10.1016/j.neuroscience.2006.03.076. View

20.

Callander G, Bathgate R . Relaxin family peptide systems and the central nervous system. Cell Mol Life Sci. 2010; 67(14):2327-41. PMC: 11115692. DOI: 10.1007/s00018-010-0304-z. View