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February 19, 2026 4:33 PM
Two Similar Enzymes Play Distinct Roles in the Brain
Two closely related enzymes, MNK1 and MNK2, have remarkably different roles in the brain, each regulating different behaviors. As researchers at the Max Delbrück Center explain in a new study published in “Molecular Psychiatry,” this knowledge could help develop more precise therapies for neurological disorders.
Structurally, MNK1 and MNK2 appear similar – both belonging to the same enzyme family and known primarily for regulating protein production within cells. This key function has positioned them as potential targets for drugs aimed at treating neurological conditions and chronic pain. But what if a medication could target only one of these enzymes?
A team led by Rosalba Olga Proce, a doctoral candidate in the “Molecular and Cellular Foundations of Behavior” group led by Dr. Hanna Hörnberg at the Max Delbrück Center, sought to answer this question. Their study, now featured in “Molecular Psychiatry,” investigated whether the two kinases – a type of enzyme – perform different functions in the brain.
The scientists found significant differences: Mice lacking MNK1 showed less interest in new objects compared to others, and later struggled to remember them. Mice without MNK2 did not exhibit these characteristics, but displayed increased interest in social interaction.
“The behavioral differences we observed suggest that each of these kinases has a specific function in the brain,” said Proce. “When developing medications, it could therefore be beneficial to address the two enzymes individually.”
The research highlights the potential for more targeted therapies for conditions impacting brain function, offering a nuanced approach to treatment development.
To understand how these behavioral changes occur, the researchers used genetically modified mice in which either the MNK1 or MNK2 gene was deactivated. They then compared the results of their behavioral tests with large-scale molecular analyses of brain tissue.
The team focused specifically on the cerebral cortex and synapses – the junctions through which nerve cells communicate. Using various methods, including proteomics, transcriptomics, and phosphoproteomics, they analyzed protein concentrations, gene expression, and protein phosphorylation patterns in both groups of mice.
They reported that mice without MNK1 had an abundance of ribosomal proteins, which play a central role in translation – the production of proteins based on messenger RNA. In mice without MNK2, however, the expression and phosphorylation of proteins involved in signal transmission at the synapses were impaired.
Notably, the team discovered that the molecular differences between the two enzymes were much more pronounced in the synapses than in samples from the entire brain. “This surprised us,” said Hörnberg. “Because this observation suggests that the kinases may have different functions in the cell body than in the synapses.”
Instead of non-specifically inhibiting both kinases, future therapies could selectively target one or the other to achieve more precise effects, Hörnberg added.
She and her colleagues now plan to identify additional molecules with which MNK1 and MNK2 interact. They also intend to investigate in more detail how the two kinases regulate the translation of messenger RNA into proteins during synaptic plasticity – when the connections between nerve cells grow stronger or weaker over time. Synaptic plasticity is the fundamental mechanism by which memory and learning function, and allows the brain to rewire itself based on experience.
The researchers’ goal is to fully understand how cells regulate their protein synthesis at the synapses, hoping to lay the foundation for more precise interventions in neurological and psychiatric disorders.
Max Delbrück Center
The Max Delbrück Center for Molecular Medicine in the Helmholtz Association lays the foundation for the medicine of tomorrow with its discoveries of today. At locations in Berlin-Buch, Berlin-Mitte, Heidelberg and Mannheim, our researchers work together interdisciplinary to decipher the complexity of different diseases at the systems level – from molecules and cells to organs and the entire organism. In scientific, clinical and industrial partnerships as well as in global networks, we work together to translate biological insights into practical applications – with the aim of identifying early indicators of disease, developing personalized treatments and ultimately preventing diseases. Founded in 1992, the Max Delbrück Center today unites a diverse workforce of around 1,800 people from more than 70 countries. We are 90 percent funded by the federal government and 10 percent by the state of Berlin.
Scientific Contact:
Dr. Hanna Hörnberg
Head of the “Molecular and Cellular Foundations of Behavior” Group
Max Delbrück Center
[email protected]
Original Publication:
DOI:10.1038/s41380-026-03483-w
More Information:
https://www.mdc-berlin.de/de/hornberg – Hörnberg AG
https://www.mdc-berlin.de/de/news/news/die-analystin-des-verhaltens – Portrait Hanna Hörnberg
Images
Mouse cerebral cortex tissue
Source: Erika Uddström
Copyright: Erika Uddström, Hörnberg lab, Max Delbrück Center
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