The researchers Alba Andrés-Bilbé and Xavier Gasull, of the Faculty of Medicine and Health Sciences, of the Neurosciences Institute of the University of Barcelona (UBNeuro) and of the Research Group in Neurophysiology of the IDIBAPS. / UB.lud, del Instituto de Neurociencias de la Universidad de Barcelona (UBNeuro) y del Grupo de Investigación en Neurofisiología del IDIBAPS. / UB
Migraine is a neurological disorder that affects 15% of the population and has a genetic, environmental and hormonal basis, but the causes are still unknown. A team of scientists has now discovered a mutation in a gene that would cause increased neuronal activity and induce migrainous pain. This study opens new ways to design future therapeutic strategies against this pathology.
Migraine causes recurrent and severe episodes of headache, and in some cases, also nausea, vomiting and photophobia. 80% of the cases are considered migraine without aura, and the remaining 20% are episodes in which the headache is preceded by transient neurological symptoms that are usually visual (migraine with aura).
Despite the high prevalence of this type of headache, “the majority of the genetic causes and pathophysiological mechanisms that are involved in it are still unknown, which makes it difficult to find effective treatments,” says Xavier Gasull.
A new work published in the journal Neuron now concludes that a mutation in the gene that codes for the ion channel TRESK – involved in the control of the excitability of neurons – causes the dysfunction of proteins that increase neuronal activity and induce pain migrainous.Experts Xavier Gasull and Alba Andrés-Bilbé from the Faculty of Medicine and Health Sciences, the Neurosciences Institute of the University of Barcelona (UBNeuro) and the Research Group in Neurophysiology at IDIBAPS participate in the study.
The control of neuronal excitability
Episodes of migraine are related to greater electrical excitability of sensory neurons. The electrical activity is controlled by proteins – the ion channels – that are responsible for facilitating or inhibiting the activation of neurons. The study, in particular, focuses on the ion channels TRESK and TREK, which are found in sensory neurons and slow down excessive neuronal activation.
According to the conclusions, a mutation in the gene that codes for the TRESK ion channel gives rise to a dysfunctional protein, which alters the ability of the channel to reduce electrical activity. In parallel, this mutation also generates another altered protein that affects the physiological function of other ion channels such as TREK1. The discovery of a mechanism by which a mutation generates two dysfunctional proteins – a process perhaps shared with other genetic pathologies – also opens up new perspectives that will have to be explored in the future.
“Paradoxically, other mutations that also eliminated the TRESK protein, but which did not cause migraine, have been described so far.” In the new study, we verified that the combination of the two factors is necessary for a greater electrical activation of the sensory neurons, what causes the pain characteristic of migraine, “says Xavier Gasull.
The work, coordinated by the researcher Guillaume Sandoz, of the University of Nice and the National Center of Scientific Research of France (CNRS), will open new ways to design future therapeutic strategies against migraine, and it is a very significant advance to know in detail the mechanisms that cause episodes of migraine with aura, unknown until now.
Perrine Royal et al. “Migraine-Associated TRESK Mutations Increase Neuronal Excitability through Alternative Translation Initiation and Inhibition of TREK” Neuron Volume 101, Issue 2, January 16, 2019, Pages 232-245.e6
Source: University of Barcelona and AGENCIA SINC