WIN55,212-2 improved cognitive impairment evaluated by BM and NORT following BFCN lesion. Credit score: British Journal of Pharmacology (2024). DOI: 10.1111/bph.17381
A College of the Basque Nation (UPV/EHU) research proves that the WIN55.212-2 drug protects the mind and reverses the preliminary cognitive injury attributable to dementia.
The UPV/EHU’s Neurochemistry and Neurodegeneration group has give you a drug that may be a potential candidate for tackling reminiscence deficits within the early phases of the illness in rodents. Analysis reveals that the drug prompts the cannabinoid neurotransmitter system (which protects the mind), and this stimulates the cholinergic system (which controls reminiscence and studying) by growing the synthesis of acetylcholine (a neurotransmitter within the mind that controls reminiscence and studying).
These outcomes, now printed within the British Journal of Pharmacology, open up a promising therapeutic method.
Analysis spanning greater than 20 years has led the UPV/EHU’s Neurochemistry and Neurodegeneration group below Dr. Rafael Rodríguez-Puertas to find a promising avenue for the event of latest therapies that enhance reminiscence in instances of cognitive impairment in neurodegenerative illnesses comparable to Alzheimer’s and Parkinson’s.
The research carried out by Dr. Marta Moreno-Rodríguez within the UPV/EHU group confirmed that the neurotransmitter receptors within the cannabinoid household and sure choline-containing lipids within the mind contribute in direction of cognitive enchancment in rats.
Rodríguez-Puertas defined, “Analyses carried out over the years on a very large sample of brain tissue from autopsies of patients who were at different stages of development of the disease enabled us, intriguingly, to see that when the first clinical symptoms of Alzheimer’s emerge, damage is found in the area that is initially affected in patients and is caused by one of the interneuronal transmission systems, the cholinergic system (which controls memory and learning and uses acetylcholine as a neurotransmitter); by contrast, we saw that another neurotransmission system, the cannabinoid system, increases.”
The crew additionally discovered that because the illness progresses, the cannabinoid system additionally finally ends up broken. “It’s as if this cannabinoid system has an initial protective response to the damage of the cholinergic system and tries to protect the brain,” he mentioned. “It is therefore a therapeutic target on which to act.”
After testing the impact of the drug WIN55.212-2, which interacts with cannabinoid receptors, on rodents within the early phases of the illness, the crew discovered “that they behaved in the same way as those without brain damage: they learned and remembered spatial orientation in the same way,” defined Moreno-Rodríguez. “You could say that in some way the drug reversed the damage or protected the brain.”
A novel approach to determine and find lipids within the mind
The analysis group was capable of perceive the mechanism of this cognitive enchancment “by using a novel technique developed and fine-tuned by the research group at the UPV/EHU and which enables the lipids in the brain to be identified and anatomically located. That way we saw that, after treatment, the activity of the cannabinoid system had increased; and also that there was an increase in the activity of the patients’ cholinergic neuronal receptors that had been damaged, and also that there was an increase in the synthesis of certain lipids containing choline, which are precursors of acetylcholine, a neurotransmitter that controls memory and learning in the brain,” defined Rodríguez-Puertas.
In different phrases, “the cannabinoid receptors were seen to be activated and the acetylcholine levels in the brain to be increased. The drug restored the cholinergic system and improved memory,” added Moreno-Rodríguez.
Rodríguez-Puertas believes that “this molecule could become a drug to treat the symptoms of dementia, at least during the initial stages of the disease, because we have already seen that the body itself, physiologically, tries to do something similar. With these pharmacological treatments we could help to enhance that effect, or perhaps even apply a mixed treatment of cannabinoid drugs with acetylcholine precursors,” he advised.
From left to proper, Gorka Pereira, Marta Moreno, Ivan Manuel, Rafael Rodriguez-Puertas, Alberto Llorente and Jonatan Martinez. Credit score: UPV/EHU
In search of related molecules to maneuver on to scientific trials
Though the outcomes of the assessments on rodents had been very promising, and the following step could be to review their toxicity and transfer on to scientific testing on people, the analysis crew has come up in opposition to the impediment that the molecule is a free-to-use molecule.
In different phrases, “it is a synthesis molecule that is widely used in experimentation; we did not synthesize it ourselves. It is not a molecule that a particular pharmaceutical company can exploit. Toxicology studies and clinical trials constitute a major investment for the pharmaceutical industry and this molecule does not offer them the possibility of future commercial exploitation,”
The crew is now working to seek out and synthesize molecules much like WIN55.212-2 that may very well be of curiosity to the pharmaceutical trade and thus pave the way in which in direction of the scientific research of this new therapeutic pathway. To this finish, they’re working in collaboration with CIC bioGUNE and the College of Vigo.
Extra info:
Marta Moreno‐Rodríguez et al, Cognitive enchancment by way of cortical cannabinoid receptors and choline‐containing lipids, British Journal of Pharmacology (2024). DOI: 10.1111/bph.17381
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College of the Basque Nation
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Molecule proven to provide cognitive enchancment in rodents with early Alzheimer’s illness (2025, January 14)
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