Scientists have discovered that learning and memory depend on the structural rather than enzymatic function of the CaMKII enzyme. This breakthrough could lead to new treatments for Alzheimer’s disease and even Down syndrome by using inhibitors that specifically target the enzyme’s enzymatic activity without affecting learning or memory. there is a possibility.
Unraveling the mechanisms of memory could pave the way for innovative treatments for Alzheimer’s disease and a variety of other neurological conditions.
Researchers at the University of Colorado Anschutz Medical Campus have made a “paradigm-changing” discovery about the mechanisms necessary for learning and memory. These discoveries have the potential to pave the way to new treatments, including: Alzheimer’s disease It could also be due to an illness or Down syndrome.
This study was recently published in the journal Nature.
For more than 30 years, researchers have believed that LTP, or long-term potentiation, important for learning and memory, requires the enzymatic action of an enzyme known as CaMKII.
However, a research team led by Dr. Uli Bayer, professor of pharmacology at the University of Colorado School of Medicine,, We discovered that LTP requires a structural rather than an enzymatic function of CaMKII.
This is important because it opens the door to the therapeutic use of a new class of inhibitors that target only the enzymatic activity of CaMKII, rather than the structural functions required for memory and learning, Bayer said. said.
Previous research from Bayer’s lab showed that inhibiting enzyme CaMKII activity protects against some of the effects of amyloid beta (Abeta) plaques in the brain, a hallmark of Alzheimer’s disease (AD). .
Researchers have discovered a group of inhibitors that protect against Aβ effects without impairing LTP, revealing that this could be useful in treating many brain diseases without causing debilitating side effects. did.
“This suggests that certain inhibitors of CaMKII activity may indeed be used chronically to treat brain diseases, including Alzheimer’s disease,” said Beyer, the study’s senior author. “This is very novel, as previously it was thought that CaMKII activity inhibitors inhibit the synaptic plasticity underlying learning and memory, making chronic use ineffective.”
Bayer said the inhibitor, if effective in humans, could offer additional benefits in combination with current Alzheimer’s disease treatment strategies.
“That’s because different mechanisms are being targeted,” he says. “We are targeting the downstream effects of Abeta. We don’t even pretend that this will be a cure, but we have the potential to dramatically reduce some of the most devastating symptoms of memory loss and learning. It’s hidden.”
The Bayer Institute is now testing whether the predictions made by that landmark paper can be used in human treatments.
Reference: “LTP induction by structural rather than enzymatic function of CaMKII” Jonathan E. Tullis, Matthew E. Larsen, Nicole L. Rumian, Ronald K. Freund, Emma E. Boxer, Carolyn Nicole Brown, Steven J. Coultrap, Written by Howard Schulman, Jason Aoto, Mark L. Delacqua, K. Ulrich Beyer, August 30, 2023. Nature.
DOI: 10.1038/s41586-023-06465-y