Scientists have discovered a potential breakthrough in Alzheimer’s disease treatment by restoring a neuron-regulating mechanism known as KCC2. This mechanism is often reduced in individuals with Alzheimer’s disease, leading to cognitive impairments. The molecule CLP290 has shown positive results in mice by activating KCC2; however, it is not suitable for human use. As a result, researchers from Laval University and the University of Lethbridge are now searching for other KCC2-activating molecules that can be safely used in humans.
Previous studies have shown that even before the onset of Alzheimer’s symptoms, there is disrupted brain activity in individuals who later develop the disease. The researchers hypothesize that the mechanism responsible for inhibiting neuronal signals, which is regulated by the neurotransmitter GABA and the KCC2 cotransporter, is disrupted in Alzheimer’s disease.
The researchers used mice expressing a manifestation of Alzheimer’s disease and found that KCC2 levels decreased in the hippocampus and prefrontal cortex, two regions affected in Alzheimer’s patients. To counteract this decrease, the researchers administered CLP290, an activator of KCC2, to the mice. They observed improved spatial memory, social behavior, and long-term protection against cognitive decline and neuronal hyperactivity.
It is important to note that the loss of KCC2 does not cause Alzheimer’s disease but rather leads to an ionic imbalance and neuronal hyperactivity. By preventing the loss of KCC2, it may be possible to slow down and even reverse certain manifestations of the disease.
Although CLP290 cannot be used in humans, the researchers are currently developing and evaluating new molecules in their laboratory. They are also exploring the effects of existing drugs used for other purposes on KCC2 activity, with the aim of finding a viable treatment for Alzheimer’s disease.
This groundbreaking research offers hope for the future of Alzheimer’s disease treatment, potentially providing a means of slowing down or reversing cognitive decline. Further studies are needed to determine the efficacy and safety of KCC2-activating molecules in humans.
Sources:
– Alzheimer’s Disease: A disease that attacks the brain, causing a decline in mental ability over time. There is no current cure, but medications can help with symptoms.
– Study: Keramidis, I., et al. “Restoring neuronal chloride extrusion reverses cognitive decline linked to Alzheimer’s disease mutations” (Brain) [No URLs]
