Alzheimer's treatment: another ray of hope?
TSPO ligands prevent and treat Alzheimer's disease in mice
LifeSciencesToday based on materials from USC Davis School of Gerontology:
Drawing closer to Alzheimer’s magic bullet... maybeImagine drug prevention, treatment, or even a complete cure for Alzheimer's disease.
The importance of such drugs cannot be overestimated – they would be the answer to the prayers of tens of millions of people.
And although science has not yet reached such heights, a new study published in The Journal of Neuroscience (Barron et al., Ligand for Translocator Protein Reverses Pathology in a Mouse Model of Alzheimer's Disease), conducted under the guidance of scientists from the Gerontology School. Davis University of Southern California (University of Southern California Davis School of Gerontology), can be called a ray of hope for a possible solution to one of the most pressing problems of modern medicine.
"Our data indicate the possibility of creating drugs that can prevent and treat Alzheimer's disease," says the lead author of the article, Professor and head of the laboratory Christian Pike (Christian Pike). "This is just data obtained in mice, but very encouraging data obtained in mice."
Scientists have studied the effect of a class of drugs, the so–called ligands (ligand molecule interacting with a complementary site of the target molecule - VM)TSPO (translocator protein, carrier protein – VM), on males of genetically modified mice with an Alzheimer's disease model, known as 3xTg-AD mice. Since one of the key effects of TSPO ligands is to enhance the synthesis of steroid hormones, it was important for the researchers to ensure that the mice would have low levels of testosterone and related hormones. Young mice were castrated, and in older animals, a decrease in testosterone levels occurred as a normal consequence of aging.
"We studied the effect of TSPO ligands on the body of young mice with an early stage of pathology and old mice with a fairly severe pathology," continues Professor Pike. "TSPO ligands mitigated pathology and improved the behavior of animals of both ages."
The most unexpected thing for Professor Pike and his colleagues was the effect of TSPO ligands on old mice. Four–time administration of the drug – once a week for four weeks - significantly mitigated the pathology associated with Alzheimer's disease in old 3xTg-AD mice and improved the animals' memory. These data suggest the possibility that TSPO ligands can, at least partially, reverse Alzheimer's disease and, therefore, have a certain therapeutic potential.
"As applied to humans, TSPO ligands are currently used in certain types of neuroimaging. More modern TSPO ligands, currently undergoing clinical trials, are planned to be used for the treatment of anxiety and other neurological disorders," explains Professor Pike. "There is a high probability that the therapeutic efficacy of TSPO ligands (similar to those used in our study) in Alzheimer's disease will be evaluated over the next few years."
In light of these discoveries, Pike and his group plan to focus on understanding exactly how TSPO ligands mitigate the pathology of Alzheimer's disease. Based on established data that these compounds have a protective effect, reducing inflammation, protecting nerve cells from damage and enhancing the synthesis of neuroactive hormones in the brain, scientists will study which of these effects is the most significant in the fight against Alzheimer's disease in order to develop new TSPO ligands based on the results obtained.
However, while acknowledging that their research opens up an exciting prospect, Professor Pike and his colleagues emphasize that they are far from thinking that the implementation of their results is something that has already happened.
"From an optimistic point of view, our discoveries are very promising and can bring tangible results in both the prevention and treatment of Alzheimer's disease," concludes Professor Pike. "From a pessimistic point of view, scientists have already developed many methods that cure Alzheimer's disease in mice, but are unable to have a significant positive effect on the condition of sick people. The most important direction that we are currently developing is the successful transfer of these results to the human body."
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