Researchers have discovered that a subunit of the ubiquitin-proteasome system acted independently of the proteasome machinery to regulate AMPA receptors, a type of glutamate receptor, at multiple steps of their life cycle. Published in the May 26, 2023, issue of Science, the findings could point to ways to target AMPA receptors. They are responsible for the majority of excitatory transmission in the central nervous system, and current drugs seeking to influence AMPA-based transmission are “good but they are not great,” Erin Schuman told BioWorld. “This regulatory particle is watching the glutamate receptor at each step.” Schuman is the director of the Max Planck Institute for Brain Research and the paper’s senior author.

Fundamental Pharma GmbH has raised €10 million (US$10.3 million) in a seed round to develop a new class of glutamate inhibitors, after uncovering a route to maintaining the protective effects of the neurotransmitter in the synapses while preventing neurotoxicity when it is released elsewhere.

Using in vivo imaging technology, investigators at the University of Utah and the University of Padua have identified a new signaling mechanism for glutamate that was linked to the onset of spreading depression or spreading depolarization, a neuronal activity pattern that plays a role in multiple neurological disease states. In mouse models of migraine, glutamate, which is the major excitatory neurotransmitter of the brain, was released in what the authors called "plumes" or puffs.

Using in vivo imaging technology, investigators at the University of Utah and the University of Padua have identified a new signaling mechanism for glutamate that was linked to the onset of spreading depression or spreading depolarization, a neuronal activity pattern that plays a role in multiple neurological disease states.