News – AU – Monash University researchers make groundbreaking discovery on how migraines are triggered

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World first: Researchers at Monash University have used cutting-edge technology to detect the progression of molecular events that lead to migraines – something that has remained a mystery until now

The discovery has closed one of the most important gaps in our understanding of the activation of migraines

The groundbreaking study, published today in the prestigious journal Science, was led by a team of researchers from the Monash Institute of Pharmaceutical Sciences (MIPS) and the recently established ARC Center for Cryo-EM of Membrane Proteins (CCeMMP)

One of the most common causes of migraines is abnormal activation levels of the target for an extremely potent vascular regulator, the calcitonin gene-related peptide (CGRP) The latest and most exciting treatments for migraines are blocking this activity, but little is known about how CGRP activates its receptor at the molecular level

In this study, researchers used significant advances in cryo-electron microscopy (cryo-EM) to show for the first time how binding of CGRP to the receptor results in receptor activation, which in turn leads to onset the migraine So far, this has simply not been possible because proteins like the CGRP receptor were too small and mobile to be captured and examined by any method

The lead author of the study, Dr Tracy Josephs, of MIPS, said, “To really understand what causes migraines, we need to be able to study structure and dynamics using unmodified forms of the receptor – this was a major technical hurdle in understanding the progression of molecular events, who link CGRP binding to activating the cellular signaling pathways that control migraine pain and one that the team has now overcome ”

“Based on the structures and data of complementary biophysical techniques, we have shown that the initial binding of CGRP to the receptor causes unexpectedly small conformational changes in the most widely used form of the receptor. It was the coordinated change in the dynamics of the external (CGRP- Binding) side of the receptor and the intracellular side, which was the key, and the visualization would not have been possible with other methods ”

Migraine affects approximately five million Australians. It is a neurological disorder that can cause several debilitating symptoms, including severe headache, nausea, vomiting, difficulty speaking, numbness or tingling, and sensitivity to light and sound

“The team has closed one of the most important gaps in our molecular understanding of how cells work – shifting the field from ‘snapshots’ at the atomic level to ‘movies’ at the atomic level,” said Dr Joseph’s

Professor Patrick Sexton, study co-lead and director of the ARC CCeMMP, said, “This is an example of the tremendous benefits of basic research in addressing large unmet medical needs”

The MIPS and ARC CCeMMP team worked with staff from the University of Tokyo, Otago University and the Hudson Institute of Medical Research

This work was supported by funding from the Australian Research Council and the National Health and Medical Research Council. High Performance Computing was provided by the Monash MASSIVE program

Migraines, Monash University, Research

News – AU – Monash University researchers make groundbreaking discovery on how migraines are triggered
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Monash University researchers make groundbreaking discovery on how migraines are triggered

Source: https://www.miragenews.com/monash-university-researchers-make-a-516595/