Science Current Events | Science News | Brightsurf.com
 

Study paves way for new therapies in fight against calcium disorders

June 01, 2016

A study led by researchers at Georgia State University provides new insights into the molecular basis of human diseases resulting from mutations in the calcium-sensing receptor (CaSR), a protein found in cell membranes.

Their findings, published Friday (May 27) in the journal Science Advances, may assist in the development of novel receptor-based therapeutics for mutations that lead to certain types of hypocalcemia and neonatal hyperparathyroidism, in addition to Alzheimer's disease and some cancers.

Calcium is abundant in the human body and participates in nearly every vital process. CaSR plays a crucial role in maintaining calcium concentration in the human body. However, the molecular basis underlying how CaSR regulates such important cell function has been unclear.

"In this study, we reported the first crystal structure of the extracellular domain of the human CaSR, which enables us to visualize a large number of residues involved in disease-associated mutations," said Jenny Yang, lead author on the paper, Distinguished University Professor and associate director of the Center for Diagnostics and Therapeutics at Georgia State.

Nearly 200 mutations and 15 polymorphisms associated with a variety of human disorders have been found in CaSR. In this study, researchers were able to map the mutations on the high-resolution CaSR structure. High-resolution structures of the CaSR are essential to gain a better understanding of the underlying mechanism in its regulated physiological functions as well as pathological activities.

"Further uncovering of the structural and functional mysteries of the calcium-sensing receptor could aid in the the development of novel receptor-based therapeutics for use in the treatment of many different diseases," Yang said.

"It is quite interesting that an unexpected small molecule occupies the native ligand binding site and functions as a high-affinity co-activator, which suggests that it may serve as a lead compound for CaSR regulators," said Jian Hu, paper co-author and assistant professor at Michigan State University.

The researchers' discoveries lay the groundwork for the development of agonists and antagonists as potential therapies for human diseases related to the CaSR.

###

This work included researchers from Georgia State, Brigham and Women's Hospital, Michigan State University and the University of Georgia, and was supported by the National Institutes of Health grants and the Georgia Research Alliance.

Georgia State University


Related Calcium-sensing Receptor Current Events and Calcium-sensing Receptor News Articles


Turning on hormone tap could aid osteoporosis fight
A potential new drug that 'opens the taps' for the release of useful hormones could stimulate new bone growth - and may eventually bring relief to osteoporosis sufferers.

Study identifies molecule essential for proper localization of blood stem cells
Scientists at the Massachusetts General Hospital (MGH) Center for Regenerative Medicine and the Harvard Stem Cell Institute (HCSI) have defined a molecule that dictates how blood stem cells travel to the bone marrow and establish blood and immune cell production.
More Calcium-sensing Receptor Current Events and Calcium-sensing Receptor News Articles

Calcium-Sensing Receptor (Endocrine Updates)

Calcium-Sensing Receptor (Endocrine Updates)
by Naibedya Chattopadhyay (Editor), Edward M. Brown (Editor)


Calcium-Sensing Receptor provides an overview of various aspects of the calcium receptor's biochemistry, physiology and pathophysiology that is suitable both for those who have been working in the field of Ca2+0-sensing as well as those who are new to this discipline.
Calcium-Sensing Receptor is the nineteenth volume published in the Endocrine Updates book series under the Series Editorship of Shlomo Melmed, MD.

Bone health Parameters and Polymorphisms of Calcium Sensing Receptors

Bone health Parameters and Polymorphisms of Calcium Sensing Receptors
by Hafsa Majid (Author), Tariq Moatter (Author), Aysha Habib (Author)


Vitamin D deficiency (VDD) has been reported from Pakistan in randomly selected healthy volunteers, patients and community females. In all studies a variable proportion (25.9%-31%) of the subjects had secondary hyperparathyroidism, as a compensatory response to VDD. However, a significant number of subjects with VDD show blunted Parathyroid hormone response. This phenomenon has been described in literature as functional hypoparathyroidism. we hypothesized that the presence of secondary hyperparathyroidism in our population could have been due to CaSR polymorphisms. In this cross-sectional study, we analyzed 140 pre-menopausal females with vitamin D deficiency for A986S and R990G CaSR gene polymorphisms. Patients bearing the GG genotype of R990G SNP had higher plasma Parathyroid hormone...

Calcium-Sensing Receptor (Endocrine Updates) (2002-12-31)

Calcium-Sensing Receptor (Endocrine Updates) (2002-12-31)
by unknown author (Author)




Calcium-Sensing Receptor (Endocrine Updates) (2002-12-31)

Calcium-Sensing Receptor (Endocrine Updates) (2002-12-31)
by Unknown (Author)




L-Amino Acid Sensing by the Calcium Sensing Receptor: Molecular and Functional Analysis

L-Amino Acid Sensing by the Calcium Sensing Receptor: Molecular and Functional Analysis
by Hee-chang Mun (Author)


The human calcium sensing receptor (hCaR) is a G-protein coupled receptor that responds to calcium ions as its principal physiological agonist. L-amino acids are allosteric activators of the cloned CaR expressed in HEK293 cells but the physiological significance of this effect has been uncertain. This book provides evidence that L-amino acids are physiologically relevant activators of endogenous CaRs. Experiments reported in this book also investigated the location of amino acid binding site of the CaR. Chimeric receptors constructed by domain shuffling between the human CaR and rat metabotropic glutamate receptor type-1 (mGlu-1) were used to localize the amino acid binding site of the CaR to its N-terminal, bilobed, Venus Fly Trap domain. Furthermore, the roles of...

Molecular Communications and Nanonetworks: From Nature To Practical Systems

Molecular Communications and Nanonetworks: From Nature To Practical Systems
by Barış Atakan (Author)


This book will introduce the concept of molecular communications and nanonetworks. The publication addresses why nanoscale communication is needed for the sophisticated nano and biotechnology applications. The text introduces the frontier applications of the molecular communication and nanonetworks. The book examines the molecular communication types called active, passive, and gap junction molecular communications. The author presents the molecular transmitter, receiver, encoding and decoding mechanisms used in these systems. Discussing the molecular communication system model and looking at the unique characteristics of practical molecular communication systems and these chemical reactions and their effects on the communication performance. Finally, the book examines the point-to-point,...

Calcium-Binding Proteins and RAGE: From Structural Basics to Clinical Applications (Methods in Molecular Biology)

Calcium-Binding Proteins and RAGE: From Structural Basics to Clinical Applications (Methods in Molecular Biology)
by Claus W. Heizmann (Editor)


A major direction in medical research leading to clinical applications  targets the regulation of intracellular calcium and the various human diseases associated with an altered homeostasis of this global second messenger. These diseases include, for example: cardiomyopathy, inflammation, brain disorders, diabetes and cancer. In Calcium-Binding Proteins and RAGE: from Structural Basics to Clinical Applications,expert researchers in the field detail many of the methods which are now commonly used to study calcium binding proteins. These methods and techniques, such as calcium-measurements, screening methods, clinical chemistry, and therapy, are generally applicable to many other areas of basic and medical research as well as to diagnostics. Written in the highly successful Methods in...

Pharmacology of G Protein Coupled Receptors, Volume 62 (Advances in Pharmacology)

Pharmacology of G Protein Coupled Receptors, Volume 62 (Advances in Pharmacology)
by S. J. Enna (Editor)


G protein coupled receptors remain the most important class of therapeutic targets in medicine. In the last 5 years, tremendous advances have been made in our understanding of the structure and mechanism of this critical family of drug targets. The present volume explores the modern experimental and conceptual framework for drug discovery for G protein coupled receptors. It explores advances in structure determination and structure-based drug design as well as new concepts of allosteric modulation, functional selectivity/biased agonism, and pharmacological chaperones. In addition, emerging drug targets such as receptor families for fatty acids, carboxylic acids, lipid mediators, etc. are included. Final chapters cover novel mechanisms of signal regulation through PDZ domains and RGS...

Ion Channels DownUnder, Volume 79 (Advances in Pharmacology)

Ion Channels DownUnder, Volume 79 (Advances in Pharmacology)
by Dominic Geraghty (Editor), Lachlan D. Rash (Editor)


Ion Channels Down Under, Volume 79 provides up-to-date information on ion channel pharmacology, their pharmacological modulators, and role in a diverse range of poorly treated medical conditions. Contributors include prominent scientists and highly-recognized experts with major accomplishments in the field of ion channel pharmacology. Topics covered include the role of ion channels in health and disease, ion channels as therapeutic targets and the molecular pharmacology of ion channels.Provides a must read book on ion channel pharmacologyContains up-to-date information on a number of ion channels, their pharmacological modulators, and their role in a diverse range of poorly treated medical conditionsContains contributions from prominent scientists and highly-recognized experts with major...

© 2017 BrightSurf.com