Sodium leak currents may reveal pathways of disease in the brain

Professor

University of Copenhagen

Stephan Pless receives DKK 20 million in funding from the Lundbeck Foundation.

Stephan Pless’ project dives into the role of an evolutionarily conserved sodium leak current in brain development and disease.

Normal brain function is based on neuronal activity, most of which originates from tiny electrical currents generated by ions moving across cell membranes. The threshold for when these minute currents result in for example action potentials, and thus cellular signaling, critically depends on the so-called resting membrane potential. This resting membrane potential is regulated by a massive protein complex, the sodium leak channelosome, which is composed of the pore-forming NALCN channel and its auxiliary subunits FAM155A, UNC79 and UNC80. Mutations in this protein complex increase or decrease channelosome activity, leading to devastating and often fatal developmental and neurological defects in humans.

The project “The role of an evolutionarily conserved sodium leak current in brain development and disease” will test and investigate how these mutations effect the structure and function of the developing nervous system.

The collaboration between the teams of Professor Stephan Pless, University of Copenhagen, and Professor Mei Zhen, University of Toronto, also aims to develop the first set of NALCN-targeting lead compounds, both small molecules and peptides. This has the potential to ultimately treat humans suffering from dysregulations in the resting membrane potential, a condition that is thus far untreatable.

Co-applicant and collaborator on the project: