Review
Cardiac & Cardiovascular Systems
Yuanqiang Li, Boyu Li, Wei-Dong Chen, Yan-Dong Wang
Summary: Cardiovascular diseases (CVDs) are the leading cause of death globally, accounting for nearly 30% of deaths worldwide annually. G-protein-coupled receptors (GPCRs) are vital in regulating cellular physiology and pathology, and play a crucial role in CVDs. Targeting GPCRs has become an important approach for the treatment of CVDs, with some GPCR antagonists serving as standard therapy.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2023)
Review
Neurosciences
Zeinab Vahidinia, Mohammad Taghi Joghataei, Cordian Beyer, Mohammad Karimian, Abolfazl Azami Tameh
Summary: Ischemic stroke currently has only one approved drug for thrombolysis, with a pressing need for new neuroprotective therapies. G-protein-coupled receptors (GPCRs) have been identified as potential targets for developing novel treatments for ischemic stroke, given their crucial roles in brain function and potential involvement in stroke pathogenesis.
MOLECULAR NEUROBIOLOGY
(2021)
Review
Endocrinology & Metabolism
Fanhua Wang, Mingyao Liu, Ning Wang, Jian Luo
Summary: This review discusses the role of G-protein coupled receptors (GPCRs) in osteoarthritis (OA), including the pathophysiological processes involved, preclinical and clinical trial data, and the challenges in developing therapies targeting GPCRs for OA.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Review
Pharmacology & Pharmacy
Kate F. Byrne, Ajay Pal, James F. Curtin, John C. Stephens, Gemma K. Kinsella
Summary: The focus of the review is on G-protein-coupled receptor (GPCR) targets, with chemokine, cannabinoid, and dopamine receptors showing promise. Further research is needed on potential targets such as MC4R, adhesion receptors, LPA, and Smo receptors to develop new drug-screening strategies for safe and effective GBM therapies.
DRUG DISCOVERY TODAY
(2021)
Review
Biochemistry & Molecular Biology
Dekel David, Ziv Bentulila, Merav Tauber, Yair Ben-Chaim
Summary: GPCRs are involved in signal transduction processes, and although they span the cell membrane, they have not been considered to be regulated by membrane potential. Recent studies, however, have shown that several GPCRs are voltage regulated. This review discusses the advances in understanding the voltage dependence of GPCRs, the suggested molecular mechanisms, and the possible physiological roles.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Dominik Michalski, Willi Reimann, Emma Spielvogel, Bianca Mages, Bernd Biedermann, Henryk Barthel, Bjorn Nitzsche, Stefan Schob, Wolfgang Hartig
Summary: This study provides the first spatio-temporal characterization of surfactant protein-G (SP-G) and neurovascular unit (NVU) elements after experimental stroke. The results show a decrease in SP-G signals in ischemic areas and inverse immunosignals of SP-G and vascular elements. In addition, morphological alterations or changed intensities were observed in signals originating from neurons, glial elements, and extracellular matrix.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biology
Ramon Cierco Jimenez, Nil Casajuana-Martin, Adrian Garcia-Recio, Lidia Alcantara, Leonardo Pardo, Mercedes Campillo, Angel Gonzalez
Summary: The study analyzed 119,069 natural variants in human olfactory receptors, revealing a significant diversity of natural variations in the olfactory gene repertoire between individuals and populations, with a considerable number of changes occurring at the structurally conserved regions. Mutations in positions linked to the conserved GPCR activation mechanism were highlighted, which could imply phenotypic variation in olfactory perception.
Review
Pharmacology & Pharmacy
Sergi Ferre, Francisco Ciruela, Carmen W. Dessauer, Javier Gonzalez-Maeso, Terence E. Hebert, Ralf Jockers, Diomedes E. Logothetis, Leonardo Pardo
Summary: The study proposes the concept of GPCR-effect assemblies (GEMMAs), which are pre-assembled before receptor activation and allow more efficient interactions between specific signaling components. This offers an alternative model to the conventional collision coupling model and explains the differential properties of GPCRs in different cellular environments.
PHARMACOLOGY & THERAPEUTICS
(2022)
Review
Chemistry, Multidisciplinary
Xin-heng He, Chong-zhao You, Hua-liang Jiang, Yi Jiang, H. Eric Xu, Xi Cheng
Summary: G protein-coupled receptors (GPCRs) are important drug targets that play crucial roles in various physiological processes. Although extensive efforts have been made in the field of structural biology, a significant number of GPCR structures remain unsolved due to their structural instability. Recently, AlphaFold2 has been developed as a tool to predict the structure models of GPCRs and other functionally important proteins. However, our evaluation reveals several differences between the predicted models and experimental structures, such as the assembly of domains, shape of ligand-binding pockets, and conformation of binding interfaces. These differences hinder the use of predicted structure models in functional studies and structure-based drug design, where reliable high-resolution structural information is required.
ACTA PHARMACOLOGICA SINICA
(2023)
Article
Biochemistry & Molecular Biology
Wojciech Pietrus, Rafal Kurczab, Dagmar Stumpfe, Andrzej J. Bojarski, Juergen Bajorath
Summary: The study showed that introducing fluorine can significantly increase ligand potency, but the effect of fluorination on affinity varies depending on the fluorination position. Fluorination of the aromatic ring at the ortho position is favorable for potency enhancement, while fluorination of aliphatic fragments more often leads to a decrease in biological activity.
Article
Chemistry, Multidisciplinary
Yunfang Xiong, Ran Ke, Qingyu Zhang, Wenjun Lan, Wanjun Yuan, Karol Nga Ieng Chan, Tom Roussel, Yifan Jiang, Jing Wu, Shuai Liu, Alice Sze Tsai Wong, Joong Sup Shim, Xuanjun Zhang, Ruiyu Xie, Nelson Dusetti, Juan Iovanna, Nagy Habib, Ling Peng, Leo Tsz On Lee
Summary: This study reports the effective modulation of a GPCR for cancer treatment using small activating RNAs (saRNAs) for the first time. The saRNAs promote the expression of MAS1, a GPCR that counteracts cancer cell proliferation and migration. By enhancing MAS1 expression, these saRNAs suppress tumorigenesis and inhibit tumor progression in multiple cancer models. This research not only provides a new strategy for cancer therapy by targeting the renin-angiotensin system, but also offers a new avenue to modulate GPCR signaling through RNA activation.
Review
Engineering, Biomedical
Yuhong Jiang, Yuke Li, Xiujuan Fu, Yue Wu, Rujing Wang, Mengnan Zhao, Canquan Mao, Sanjun Shi
Summary: The translation article introduces the interaction between G protein-coupled receptors (GPCRs) and nanotechnology, as well as how nanotechnology can improve the efficacy and safety of GPCR-related drugs. Nanotechnology can encapsulate GPCR ligands to construct synthetic nano-GPCRs and precisely initiate sustained endosomal signal transduction through nanoparticles. Moreover, nanoparticles can enhance the potency of delivery systems by actively targeting specific cells through ligand-receptor binding and receptor-dependent endocytosis.
ACTA BIOMATERIALIA
(2023)
Review
Cardiac & Cardiovascular Systems
Alyssa Grogan, Emilio Y. Lucero, Haoran Jiang, Howard A. Rockman
Summary: G protein-coupled receptors (GPCRs) play key roles in cardiac health and disease, and are targeted for the treatment of cardiovascular diseases. Recent advancements in understanding GPCR signaling, regulation, and pharmacological properties have provided valuable insights.
CARDIOVASCULAR RESEARCH
(2023)
Review
Endocrinology & Metabolism
Siyuan Shen, Chang Zhao, Chao Wu, Suyue Sun, Ziyan Li, Wei Yan, Zhenhua Shao
Summary: GPCRs, as the largest family of transmembrane proteins, regulate various physiological processes. However, their complicated signal transduction pathways and difficulties in drug development have presented challenges. By identifying new ligands that bind to allosteric sites, safer drugs for treating various diseases can be designed.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Pharmacology & Pharmacy
Kemeng Zhao, Pengwei Wang, Xiaoguang Tang, Na Chang, Haonan Shi, Longfei Guo, Bingyi Wang, Pengfei Yang, Tiantian Zhu, Xinghua Zhao
Summary: Stroke is caused by ruptured or blocked cerebral blood vessels and subsequent disruption of brain blood circulation, resulting in rapid neurological deficits. The majority of stroke cases are ischemic strokes. Current treatments for ischemic stroke, such as t-PA thrombolytic therapy and surgical thrombectomy, can paradoxically lead to ischemia-reperfusion injury, exacerbating brain damage. Minocycline, a semi-synthetic tetracycline antibiotic, has demonstrated a wide range of neuroprotective effects independent of its antibacterial activity. In this article, we summarize the mechanisms underlying the protective effects of minocycline against cerebral ischemia-reperfusion injury, including modulation of oxidative stress, inflammatory response, excitotoxicity, programmed cell death, and blood-brain barrier injury. We also discuss the role of minocycline in alleviating stroke-related complications, providing a theoretical basis for its clinical application in cerebral ischemia-reperfusion injury.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Review
Anesthesiology
Hongtao Liu, Katharina M. Busl, Sylvain Dore
Summary: Dexmedetomidine (DEX), an alpha(2)-adrenergic agonist, has various beneficial effects such as anti-inflammation, antioxidation, and anticell death. It has shown potential as a protective therapy for patients with subarachnoid hemorrhage (SAH) by maintaining stable intracerebral homeostasis, repairing blood-brain barrier damage, and preventing vasospasm and cortical spreading depolarization. However, more clinical trials and translational research are needed to further evaluate its effectiveness.
JOURNAL OF NEUROSURGICAL ANESTHESIOLOGY
(2022)
Article
Clinical Neurology
Aaron M. Gusdon, Jude Savarraj, Liang Zhu, Peeyush K. Thankamani Pandit, Sylvain Dore, Devin W. McBride, HuiMahn A. Choi, Spiros L. Blackburn
Summary: This study revealed that patients with the HP 2-2 genotype showed higher levels of inflammatory cytokines at all time points compared to those with HP 1-1/1-2 genotypes. However, there were no significant differences in functional outcomes between the two groups. These findings may guide future research in identifying markers for functional prognosis or treatment targets.
CURRENT NEUROVASCULAR RESEARCH
(2021)
Review
Biochemistry & Molecular Biology
Ayon Bhattacharya, Rani Ashouri, Madison Fangman, Alexandra Mazur, Timothy Garett, Sylvain Dore
Summary: Soluble receptors, formed through cleavage from membrane-bound counterparts, play key roles in inflammation, oxidative stress, and stroke management. Their unique structures enable them to modulate receptor signaling and exhibit dual functions in cell protection.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell & Tissue Engineering
Janak Gaire, Justin A. Varholick, Sabhya Rana, Michael D. Sunshine, Sylvain Dore, W. Brad Barbazuk, David D. Fuller, Malcolm Maden, Chelsey S. Simmons
Summary: The spiny mouse is an exciting research organism due to its remarkable scarless healing abilities in various tissues beyond the skin, which could shed light on numerous clinically relevant human diseases. However, there are challenges in working with this emerging research organism that require future strategies and methods.
NPJ REGENERATIVE MEDICINE
(2021)
Editorial Material
Pharmacology & Pharmacy
Alexandra Mazur, Madison Fangman, Rani Ashouri, Arianna Arcenas, Sylvain Dore
EXPERT OPINION ON THERAPEUTIC TARGETS
(2021)
Review
Biochemistry & Molecular Biology
Daniel A. Lichlyter, Zachary A. Krumm, Todd A. Golde, Sylvain Dore
Summary: Ischaemic neurovascular stroke is a major cause of death in developed countries, and the corticotropin-releasing factor (CRF) family of neuropeptides plays an important role in the pathology of acute neurovascular injury. However, there is still limited understanding of the pathway, temporality, and systemic impact of CRF signaling and stress biology in the progression of neurovascular injury. This review aims to investigate the potential benefits of a CRF antibody in modulating CRF and corticotropin-releasing factor receptor 1 signaling, glucocorticoids, and autonomic nervous system activity, and compare the modulation of CRF and HPA axis activity in neuropsychiatric diseases and post-stroke outcomes with lessons learned from antibody therapies in neurodegenerative diseases.
Article
Clinical Neurology
Ben Gaastra, Sheila Alexander, Mark K. Bakker, Hemant Bhagat, Philippe Bijlenga, Spiros Blackburn, Malie K. Collins, Sylvain Dore, Christoph Griessenauer, Philipp Hendrix, Eun Pyo Hong, Isabel C. Hostettler, Henry Houlden, Koji IIhara, Jin Pyeong Jeon, Bong Jun Kim, Munish Kumar, Sandrine Morel, Paul Nyquist, Dianxu Ren, Ynte M. Ruigrok, David Werring, Ian Galea, Diederik Bulters, Will Tapper
Summary: This article introduces a two-stage genome-wide association study on susceptibility loci for clinical outcome after aneurysmal subarachnoid hemorrhage (aSAH). Only a small fraction of the variation in clinical outcome can be explained by known clinical, demographic, and imaging variables, suggesting the involvement of unknown factors. Understanding the genetic determinants of outcome is crucial for improving prognostic modeling, stratifying patients in clinical trials, and developing novel treatment strategies.
TRANSLATIONAL STROKE RESEARCH
(2022)
Article
Genetics & Heredity
Olivia Edwards, Alicia Burris, Josh Lua, Diana J. Wilkie, Miriam O. Ezenwa, Sylvain Dore
Summary: This review examines the role of haptoglobin genetic polymorphism and stroke occurrence in the pathophysiology of sickle cell disease. It suggests that further research should be conducted to explore potential clinical advancements in gene therapy and Hp infusions.
Review
Neurosciences
Sean Sachdeva, Sushmita Persaud, Milani Patel, Peyton Popard, Aaron Colverson, Sylvain Dore
Summary: This review discusses the effects of music/sound on blood-brain barrier permeability and meningeal lymphatic clearance, highlighting its potential positive impact on brain and body functions. However, there is limited knowledge regarding the systematic investigation and outcomes of using music/sound in medical interventions. Further research is needed to explore the potential of music/sound in healthcare.
Article
Clinical Neurology
Ben Gaastra, Sheila Alexander, Mark K. Bakker, Hemant Bhagat, Philippe Bijlenga, Spiros L. Blackburn, Malie K. Collins, Sylvain Dore, Christoph J. Griessenauer, Philipp Hendrix, Eun Pyo Hong, Isabel C. Hostettler, Henry Houlden, Koji IIhara, Jin Pyeong Jeon, Bong Jun Kim, Jiang Li, Sandrine Morel, Paul Nyquist, Dianxu Ren, Ynte M. Ruigrok, David Werring, Will Tapper, Ian Galea, Diederik Bulters
Summary: This study identified 157 genetic variants associated with outcomes after aneurysmal subarachnoid haemorrhage (aSAH) through a genome-wide association study, with one variant in the SPNS2 gene achieving genome-wide significance. Validation of these findings will provide significant insights into the pathophysiology of outcomes after aSAH and may have implications for treatment.
TRANSLATIONAL STROKE RESEARCH
(2023)
Article
Neurosciences
Ben Gaastra, Dianxu Ren, Sheila Alexander, Issam A. Awad, Spiros Blackburn, Sylvain Dore, Dan Hanley, Paul Nyquist, Diederik Bulters, Ian Galea
Summary: This study demonstrates the high correlation between the modified Rankine Scale (mRS) and Glasgow Outcome Scale (GOS) and establishes the optimal dichotomization threshold for agreement. The study also provides a method for interconversion and finds that conversion from mRS to GOS is better than the reverse direction.
JOURNAL OF STROKE & CEREBROVASCULAR DISEASES
(2022)
Review
Clinical Neurology
Basma Mohamed, Keerthi Yarlagadda, Zachary Self, Alexandra Simon, Frank Rigueiro, Maryam Sohooli, Stephan Eisenschenk, Sylvain Dore
Summary: Sleep-disordered breathing, including obstructive sleep apnea, is a common sequela and risk factor for stroke. This scoping review investigates the relationship between obstructive sleep apnea and stroke outcomes, highlighting the pathophysiology and the importance of treatment. Understanding this relationship has implications for the clinical management and prognosis of patients with acute ischemic stroke.
TRANSLATIONAL STROKE RESEARCH
(2023)
Meeting Abstract
Endocrinology & Metabolism
Marietta Zille, Jaroslaw Aronowski, Nicole A. Terpolilli, Sylvain Dore
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2022)
Review
Neurosciences
Kiana Saadatmand, Saba Khan, Quaratulain Hassan, Raymond Hautamaki, Rani Ashouri, Josh Lua, Sylvain Dore
Summary: Vitamin D supplementation has been shown to improve patient outcomes in various illnesses, while deficiencies may worsen symptoms. Research on the effects of vitamin D in traumatic brain injury is still in its early stages, with much to be learned about its potential benefits.
TRANSLATIONAL NEUROSCIENCE
(2021)
Review
Chemistry, Multidisciplinary
Flavia Cavicchioli, Izzy M. Cesarotti, Madison Fangman, Josh Lua, Raymond Hautamaki, Sylvain Dore
Summary: Carbon monoxide, known for its toxicity, has potential therapeutic applications as a gasotransmitter with anti-inflammatory and antioxidant effects. The Nrf2/HO1 pathway is a key target for therapy development due to its role in CO release. Current forms of CO therapy include inhaled CO, carbon monoxide-releasing molecules, and hybrid carbon monoxide-releasing molecules.
CHEMISTRY-SWITZERLAND
(2021)
Article
Neurosciences
Yang He, Jun Tang, Meng Zhang, Junjie Ying, Dezhi Mu
Summary: This study investigated the protective effects and mechanisms of human placenta derived mesenchymal stem cells (hPMSCs) transplantation in a rat model of hypoxic-ischemic encephalopathy (HIE). The results showed that hPMSCs transplantation reduced apoptosis and improved long-term neurological prognosis. Furthermore, the downregulation of Sema 3A/NRP-1 expression and activation of the PI3K/Akt/mTOR signaling pathway played a key role in the protective effects of hPMSCs.
Article
Neurosciences
Emily L. Isenstein, Edward G. Freedman, Jiayi Xu, Ian A. DeAndrea-Lazarus, John J. Foxe
Summary: This study evaluated electrophysiological discrimination of parametric somatosensory stimuli in healthy young adults to understand how the brain processes the duration of tactile information. The results showed that participants did not electrophysiologically discriminate between 100 and 115 ms, but they exhibited distinct electrophysiological responses when the deviant stimuli were 130, 145, and 160 ms. These findings contribute to a better understanding of tactile sensitivity in different clinical conditions.
Article
Neurosciences
Juliana R. Souza, Ludmila Lima-Silveira, Daniela Accorsi-Mendonca, Benedito H. Machado
Summary: This study demonstrates that A2A receptors play a crucial role in modulating synaptic transmission in the NTS neurons and are required for the enhancement of glutamatergic transmission observed under short-term sustained hypoxia conditions.
Article
Neurosciences
Miki Hashizume, Rina Ito, Rie Suge, Yasushi Hojo, Gen Murakami, Takayuki Murakoshi
Summary: The basolateral amygdaloid complex (BLA) is closely involved in the formation of emotional memories, including both aversive memory and contextual fear memory. Acute sleep deprivation (SD) disrupts the acquisition of tone-associated fear memory in juvenile rats, but has no significant effect on contextual fear memory. Slow network oscillation in the amygdala contributes to the formation of amygdala-dependent fear memory in relation to sleep.
Article
Neurosciences
Qunxian Wang, Shipeng Guo, Dongjie Hu, Xiangjun Dong, Zijun Meng, Yanshuang Jiang, Zijuan Feng, Weihui Zhou, Weihong Song
Summary: GSDME plays a crucial role in the pathogenesis of Alzheimer's disease by regulating the switch from apoptosis to pyroptosis and participating in neuroinflammatory response. Knockdown of GSDME has been shown to improve cognitive impairments, indicating that GSDME could be a therapeutic target for Alzheimer's disease.
