| First Author | León R | Year | 2023 |
| Journal | Front Aging Neurosci | Volume | 15 |
| Pages | 1180987 | PubMed ID | 37358955 |
| Mgi Jnum | J:346947 | Mgi Id | MGI:7494652 |
| Doi | 10.3389/fnagi.2023.1180987 | Citation | Leon R, et al. (2023) c-Abl tyrosine kinase down-regulation as target for memory improvement in Alzheimer's disease. Front Aging Neurosci 15:1180987 |
| abstractText | BACKGROUND: Growing 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/PSEN1DeltaE9 (APP/PS1) mouse model for AD. METHODS: We 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. RESULTS: We 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. DISCUSSION: Our 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. |
