Review
Biochemistry & Molecular Biology
Adriano Bonura, Nicoletta Brunelli, Marilena Marcosano, Gianmarco Iaccarino, Luisa Fofi, Fabrizio Vernieri, Claudia Altamura
Summary: The calcitonin gene-related peptide (CGRP) is a neuropeptide with complex systemic impact beyond nociception. It plays a crucial role in vasodilation, inflammation, intestinal motility, and apoptosis. CGRP has contradictory effects, acting as a potent vasodilator in the cardiovascular system but not inducing arterial hypertension. It also exhibits both anti-inflammatory and pro-inflammatory effects as an immunomodulator.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Food Science & Technology
Haoran Chen, Xiaofen Qi, Kaifang Guan, Yuxiang Gu, Rongchun Wang, Qiming Li, Ying Ma
Summary: The study showed that peptides from alpha-lactalbumin hydrolysate could improve lipid metabolism in HepG2 cells, with P2 and P8 being more effective in enhancing intracellular TG and PPAR alpha levels. These peptides acted as PPAR alpha ligands to regulate lipid metabolism-related gene expression, showing promise in ameliorating obesity.
JOURNAL OF FUNCTIONAL FOODS
(2021)
Article
Plant Sciences
Lina Duan, Juan Manuel Perez-Ruiz, Francisco Javier Cejudo, Jose R. Dinneny
Summary: The study reveals the essential role of CYP38-dependent photosynthetic activity in supporting root growth, partly through the synergistic effects of sucrose and auxin.
Article
Anesthesiology
Tarique Benbow, Maryam Ranjbar Ekbatan, Grace Hong Yue Wang, Felisha Teja, Fernando G. Exposto, Peter Svensson, Brian E. Cairns
Summary: This study explored the effects of monosodium glutamate (MSG) on the behavior and physiology of rats. The results showed that MSG induced headache-like and nausea-like behaviors, and increased plasma glutamate and calcitonin gene-related peptide concentrations. This model may contribute to the research on the mechanism and treatment of primary headache disorders such as migraine.
Article
Biochemistry & Molecular Biology
Pau Caravaca-Fuentes, Cristina Camo, Angel Oliveras, Aina Baro, Jesus Frances, Esther Badosa, Marta Planas, Lidia Feliu, Emilio Montesinos, Anna Bonaterra
Summary: The paper describes the design and synthesis of peptide conjugates BP358 and BP359, with BP358 demonstrating strong antimicrobial activity against six plant pathogenic bacteria in vitro, without hemolytic or toxic effects on tobacco leaves. BP358 also induced overexpression of plant defense-related genes and effectively controlled fire blight infections in pear plants.
Article
Pharmacology & Pharmacy
Jiang-Yan Liu, Hao-Yan Huang, Wei Sun, Huan Yu, Leshuai W. Zhang, Renyu Huang, Xiaojuan Lu, Zhao Xu, Heyun Yu, Qing-Ri Cao
Summary: By modifying solid lipid nanoparticles with anti-phagocytosis peptide and CTC recognition peptide, the ability to capture CTCs is improved while reducing systemic clearance.
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Yue Wang, Ruiwei Ye, Liming Fan, Xin Zhao, Linxue Li, Hao Zheng, Yan Qiu, Xiuxia He, Yiming Lu
Summary: The study demonstrates that an anti-tumor necrosis factor-alpha (TNF-α) peptide, SN1-13, has anti-inflammatory activity by inhibiting TNF-α-induced cytotoxicity and blocking TNF-α-triggered signaling pathways. Molecular docking analysis also suggests that SN1-13 can disrupt the binding between TNF-α and its receptors, TNFR1 and TNFR2. These findings indicate that SN1-13 has potential as a therapeutic peptide for TNF-α-mediated inflammatory diseases.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Article
Anesthesiology
David A. C. Messerer, Thomas Datzmann, Anke Baranowsky, Leandra Peschel, Andrea Hoffmann, Michael Groeger, Michael Amling, Martin Wepler, Benedikt L. Nussbaum, Shan Jiang, Paul Knapstein, Antonia Donat, Enrico Calzia, Peter Radermacher, Johannes Keller
Summary: The study found that CGRP receptor antagonism with olcegepant was not beneficial in a porcine model of polymicrobial sepsis, which closely mimics human sepsis.
BRITISH JOURNAL OF ANAESTHESIA
(2022)
Article
Cell Biology
Shrivani Sriskanthadevan-Pirahas, Michael J. Turingan, Joel S. Chahal, Erin Thorson, Shahoon Khan, Abdul Qadeer Tinwala, Savraj S. Grewal
Summary: Animals must adapt their growth to fluctuations in nutrient availability through interorgan communication in nutrient-sensing tissues. This study reveals how the reprogramming of adipose mitochondria controls whole-body growth in Drosophila larvae. Dietary nutrients alter fat-body mitochondrial morphology and lower their bioenergetic activity, leading to rewiring of fat-body glucose metabolism. Reprogramming mitochondrial metabolism in one nutrient-sensing tissue can couple nutrient availability to whole-body growth by modulating secretion of specific peptides and insulin signaling.
Article
Chemistry, Multidisciplinary
Shoko Fujita, Izuru Kawamura, Ryuji Kawano
Summary: Nanopore sensing is a popular technique for rapid, simple, and label-free single-molecule detection. In order to apply this technology to a wide range of targets, such as polypeptides, nanopores with suitable size and structure are required. Researchers have designed a de novo fl-barrel peptide nanopore (SVG28) that is stable and monodisperse in size. They used a cell-free synthesis system to express hydrophilic variants of SVG28, which formed monodisperse nanopores with a diameter smaller than that of SVG28. This cell-free synthesizable peptide nanopore has the potential to enable systematic customization and comprehensive sequence screening of nanopores.
Article
Gastroenterology & Hepatology
Yang Liu, Xin Dou, Wei-Yu Zhou, Meng Ding, Ling Liu, Ruo-Qi Du, Liang Guo, Shu-Wen Qian, Yan Tang, Qi-Qi Yang, Dong-Ning Pan, Xiao-Ying Li, Yan Lu, Jin-Ke Cheng, Qi-Qun Tang
Summary: The liver-specific knockout of SENP2 in mice showed resistance to high-fat diet-induced hepatic steatosis and obesity, upregulation of genes involved in fatty acid oxidation, and downregulation of genes in lipogenesis. Additionally, ablation of hepatic SENP2 activated thermogenesis in adipose tissues, promoting energy homeostasis. FGF21 was identified as a key factor in maintaining metabolic balance in SENP2 knockout mice.
Article
Ophthalmology
Kofi Asiedu, Maria Markoulli, Stefano Bonini, Anthony J. Bron, Murat Dogru, Natalie Kwai, Ann Poynten, Mark D. P. Willcox, Arun Krishnan
Summary: Ocular surface neuropeptides are crucial molecules for maintaining ocular surface integrity and communication between the nervous and immune systems. They play significant roles in diseases by abnormal synthesis, defective receptor signaling, or both.
EXPERIMENTAL EYE RESEARCH
(2022)
Article
Pharmacology & Pharmacy
Tamara Lutzenburg, Nele Burdina, Matthias S. Scholz, Ines Neundorf
Summary: Cell-penetrating peptides (CPPs) are used to increase the intracellular accumulation of cargoes by forming stable secondary structures at the outer surface of the plasma membrane. Incorporation of hydrophobic moieties like carboranes (CBs) can alter the lipophilicity of peptides and enhance secondary structure formation, leading to potential applications in nucleic acid delivery.
Article
Multidisciplinary Sciences
Mark A. B. Kreutzberger, Shengyuan Wang, Leticia C. Beltran, Abraham Tuachi, Xiaobing Zuo, Edward H. Egelman, Vincent P. Conticello
Summary: PSMs are peptide-based virulence factors that can self-assemble into fibrillar species and nanotubes. Structural analysis reveals the complexity and polymorphism of PSM derivatives.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Rheumatology
Tazio Maleitzke, Alexander Hildebrandt, Jerome Weber, Tamara Dietrich, Jessika Appelt, Denise Jahn, Dario Zocholl, Anke Baranowsky, Georg N. Duda, Serafeim Tsitsilonis, Johannes Keller
Summary: The study revealed an inflammatory and bone-protective role of alpha CGRP in CAIA, showing that alpha CGRP enhances joint inflammation while controlling bone remodelling. This suggests that alpha CGRP inhibitors, currently used for migraine treatment, may have an impact on RA progression and require further clinical investigation.
Review
Pharmacology & Pharmacy
Tayla A. Rees, Erica R. Hendrikse, Debbie L. Hay, Christopher S. Walker
Summary: In addition to CGRP, calcitonin family peptides may be therapeutically useful in treating migraines and other pain disorders. Their localization in peripheral pain pathways could play a role in migraines and pain.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Review
Pharmacology & Pharmacy
Michael L. Garelja, Christopher S. Walker, Debbie L. Hay
Summary: The development of drugs targeting the CGRP system has been a major breakthrough in migraine management. These drugs can be classified into antibodies and receptor antagonists, with receptor antagonists further divided into small molecule antagonists and antibody antagonists. While antagonists are most potent at the CGRP receptor, they may also show antagonism at the AMY(1) receptor, indicating the need for further research.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Michael L. Garelja, Rebekah L. Bower, Margaret A. Brimble, Shanan Chand, Paul W. R. Harris, Muhammad Aqfan Jamaluddin, Jakeb Petersen, Andrew Siow, Christopher S. Walker, Debbie L. Hay
Summary: The pharmacology of the mouse CLR/CTR and RAMPs receptors differs from that of humans, with mouse receptors showing reduced discrimination between ligands, posing challenges for interpreting data in preclinical models and translating findings from mice to humans. New ligands are needed to differentiate between these complexes.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Zoe Tasma, Andrew Siow, Paul W. R. Harris, Margaret A. Brimble, Debbie L. Hay, Christopher S. Walker
Summary: The PACAP-responsive receptors exhibit varied pharmacological profiles but activate signaling in a similar manner. The PAC(1s) receptor can act as a dual receptor for VIP and PACAP. The effectiveness of blocking a signaling pathway can be influenced by the endogenous PACAP family agonist present, with PACAP-38 showing less antagonism compared to PACAP-27 and VIP.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Clinical Neurology
Erica R. Hendrikse, Tayla A. Rees, Zoe Tasma, Christelle Le Foll, Thomas A. Lutz, Andrew Siow, Peter J. Wookey, Christopher S. Walker, Debbie L. Hay
Summary: This study examined the expression of the calcitonin receptor protein subunit in the rodent brain and found that it was present in several brain regions relevant to migraine. The findings suggest a potential link between the calcitonin gene-related peptide and migraine, but further research is needed to understand the functional consequences of calcitonin receptor expression.
Article
Multidisciplinary Sciences
Jianjun Cao, Matthew J. Belousoff, Yi-Lynn Liang, Rachel M. Johnson, Tracy M. Josephs, Madeleine M. Fletcher, Arthur Christopoulos, Debbie L. Hay, Radostin Danev, Denise Wootten, Patrick M. Sexton
Summary: The structure and dynamics of AMYRs with amylin and CT were studied, revealing the role of RAMP and the presence of a bypass motif. The binding mechanism of CT-based peptides to AMYRs is distinct from that of amylin-based peptides. This finding has implications for the development of AMYR therapeutics.
Review
Clinical Neurology
Michael L. Garelja, Debbie L. Hay
Summary: A comprehensive understanding of the pharmacology and relationship to migraine of the calcitonin peptide family of receptors is important in the development of new anti-migraine drugs and the interpretation of the mechanism of action of current drugs.
Article
Biochemistry & Molecular Biology
Zoe Tasma, Andrew Siow, Paul W. R. Harris, Margaret A. Brimble, Simon J. O'Carroll, Debbie L. Hay, Christopher S. Walker
Summary: This study validated commercially available antibodies and used them to detect PACAP-responsive receptors in the trigeminal ganglia. Antibodies that could differentiate between receptor splice variants were identified, and expression of multiple receptors in neuronal and glial-like cells was observed. These findings suggest that these receptors are potential targets for migraine treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Erica R. R. Hendrikse, Tayla A. A. Rees, Zoe Tasma, Michael L. L. Garelja, Andrew Siow, Paul W. R. Harris, John B. B. Pawlak, Kathleen M. M. Caron, Elizabeth S. S. Blakeney, Andrew F. F. Russo, Levi P. P. Sowers, Thomas A. A. Lutz, Christelle Le Foll, Christopher S. S. Walker, Debbie L. L. Hay
Summary: This study evaluated antibodies for the detection of RAMP1 protein and found that two antibodies could detect a RAMP1-like band in rodent brain tissue, but with cross-reactivity to other proteins. The anatomical localization of RAMP1 in the brain could not be determined, highlighting the need for comprehensive validation of RAMP1 antibodies. This research has broader implications for GPCR/ligand pairings beyond the field of CGRP.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Editorial Material
Biochemistry & Molecular Biology
Tayla A. A. Rees, Debbie L. L. Hay, Christopher S. S. Walker
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Pharmacology & Pharmacy
Ilana B. Kotliar, Emily Lorenzen, Jochen M. Schwenk, Debbie L. Hay, Thomas P. Sakmar
Summary: G protein-coupled receptors (GPCRs) interact with a variety of membrane proteins, but the extent and mechanisms of these interactions are not well understood. RAMPs, a class of GPCR-interacting proteins, have been extensively studied. Recent research suggests that GPCR-RAMP interactions may be more widespread than previously thought. This review summarizes the latest techniques for discovering GPCR-RAMP interactions and their functional consequences, and discusses future research prospects.
PHARMACOLOGICAL REVIEWS
(2023)
Review
Physiology
Andrew F. Russo, Debbie L. Hay
Summary: Calcitonin gene-related peptide (CGRP) is a neuropeptide with diverse physiological functions. It acts through various receptors and is associated with disease states such as migraine. Therapeutics targeting the CGRP axis have shown success in bench-to-bedside translation. This review provides a comprehensive overview of CGRP's regulation, expression, physiological actions, and potential therapeutic targeting in various systems and diseases.
PHYSIOLOGICAL REVIEWS
(2023)
Article
Medicine, General & Internal
Sasha A. Philbert, Sarah J. Schoenberger, Jingshu Xu, Stephanie J. Church, Richard D. Unwin, Garth J. S. Cooper
Summary: The study found that hippocampal copper levels were significantly elevated in patients with T2D, similar to untreated cases of Wilson's disease (WD), while hippocampal copper levels were markedly deficient in patients with sAD. These results suggest that hippocampal copper may play a role in the neurodegeneration and cognitive impairment in T2D, and therapeutic approaches targeting copper reduction, similar to those used in WD, may be applicable to patients with T2D.
Article
Pharmacology & Pharmacy
Michael L. Garelja, Tyla I. Alexander, Amy Bennie, Mhairi Nimick, Jakeb Petersen, Christopher S. Walker, Debbie L. Hay
Summary: This study demonstrates that erenumab can antagonize both CGRP and AMY(1) receptors, providing insights into the clinical profile of erenumab.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Medicine, General & Internal
Melissa Schole, Stefano Patassini, Jingshu Xu, Garth J. S. Cooper
Summary: This study observed alterations in metallomic profiles in the Huntington's disease (HD) brain, which may contribute to various pathogenic mechanisms. Selenium supplementation could offer a potential therapeutic pathway for HD treatment, as selenium deficiency is widespread in regions with differing levels of neurodegeneration.
