Unlocking the Memory Vault: Targeting c-Abl for Alzheimer’s Memory Improvement

Published on June 5, 2023

Imagine your brain as a vast library of memories, brimming with books waiting to be discovered. In the realm of Alzheimer’s disease (AD), the non-receptor tyrosine kinase known as c-Abl is like a mischievous librarian, sneaking in and causing chaos. However, scientists have aimed their sights on this troublemaker, exploring ways to quiet its actions for the benefit of memory. Through studies in an AD mouse model, researchers used genetic manipulation and a special drug called neurotinib to block c-Abl. The results were extraordinary! The mice with diminished c-Abl levels or those fed with neurotinib showed improvements in cognitive tasks related to memory. They remembered the whereabouts of objects, found escape routes faster, and showcased enhanced learning abilities. Furthermore, reduced amyloid plaques (a hallmark of AD), less inflammation, and greater preservation of neurons were observed in the hippocampus. Can you believe it? Taming c-Abl appears to be a promising strategy for AD therapy! If you’re curious about diving deeper into the science behind these exciting findings, explore the research article linked below!

BackgroundGrowing evidence suggests that the non-receptor tyrosine kinase, c-Abl, plays a significant role in the pathogenesis of Alzheimer’s disease (AD). Here, we analyzed the effect of c-Abl on the cognitive performance decline of APPSwe/PSEN1ΔE9 (APP/PS1) mouse model for AD.MethodsWe used the conditional genetic ablation of c-Abl in the brain (c-Abl-KO) and pharmacological treatment with neurotinib, a novel allosteric c-Abl inhibitor with high brain penetrance, imbued in rodent’s chow.ResultsWe found that APP/PS1/c-Abl-KO mice and APP/PS1 neurotinib-fed mice had improved performance in hippocampus-dependent tasks. In the object location and Barnes-maze tests, they recognized the displaced object and learned the location of the escape hole faster than APP/PS1 mice. Also, APP/PS1 neurotinib-fed mice required fewer trials to reach the learning criterion in the memory flexibility test. Accordingly, c-Abl absence and inhibition caused fewer amyloid plaques, reduced astrogliosis, and preserved neurons in the hippocampus.DiscussionOur results further validate c-Abl as a target for AD, and the neurotinib, a novel c-Abl inhibitor, as a suitable preclinical candidate for AD therapies.

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