Scientists have developed a new technique that could eventually lead to new potential treatments for Alzheimer’s disease. improved the symptoms.
A protein called p38 was previously linked to the development of Alzheimer’s disease, so it’s not surprising that scientists have explored this as a drug target for the disease. Drug candidates that inhibit p38 have undergone several stages of clinical trials, but unfortunately have shown limited efficacy and undesirable side effects.
So, in a new study, Korean researchers switched their focus to another form of the protein: when p38 undergoes a modification process called phosphorylation, it becomes the active form of the protein known as p-p38. By targeting this version instead, treatments could be more specific, resulting in fewer side effects and hopefully greater efficacy.
After screening various compounds that target p-p38, the team identified a compound called PRZ-18002. This was effective not only in inhibiting proteins, but also in degrading them. Importantly, it was highly selective for p-p38 only. The team tested against 96 similar protein kinases, including p38, and found that it remained on target.
When tested in a mouse model of Alzheimer’s disease, the team found that PRZ-18002 successfully downregulated the p38 pathway. This improved the animals’ cognitive abilities, such as spatial reasoning, and reduced disease-associated brain chemicals, such as the accumulation of amyloid-beta plaques.
Of course, this research is just beginning. Results in mice do not always translate to humans, and this technique, like previous techniques, is likely to fail in clinical trials. But it’s an interesting new avenue.
A study was published in a journal ACS Central Science.
Source: American Chemical Society
