Ji Eunbyul, Pal Apala, Claybourne Quia C, Michel Marc, Munk Rachel, McDevitt Ross A, Cui Chang-Yi, Gorospe Myriam
Laboratory of Genetics and Genomics, National Institute on Aging (NIA) Intramural Research Program (IRP), National Institutes of Health (NIH), Baltimore, Maryland, USA.
Comparative Medicine Section, National Institute on Aging (NIA) Intramural Research Program, National Institutes of Health (NIH), Baltimore, Maryland, USA.
Aging Cell. 2025 Jun;24(6):e70080. doi: 10.1111/acel.70080. Epub 2025 May 12.
Alzheimer's disease (AD) is the most common neurodegenerative pathology in older persons. The accumulation of amyloid β (Aβ) plaques is a major contributor to AD development. The RNA-binding protein HuD/ELAVL4 has been implicated in the formation of Aβ plaques, but its role in AD is unclear. Here, we report that ablation of HuD from CAMK2A neurons (HuDcKO) in the 5xFAD mouse model of AD results in a significant reduction of Aβ plaques and the alleviation of some AD-associated behaviors. Given the lack of effective therapies for AD, we propose that reducing HuD levels or function can contribute to diminishing Aβ plaque formation and AD-associated pathology.
阿尔茨海默病（AD）是老年人中最常见的神经退行性病变。淀粉样β（Aβ）斑块的积累是AD发展的主要促成因素。RNA结合蛋白HuD/ELAVL4与Aβ斑块的形成有关，但其在AD中的作用尚不清楚。在此，我们报告在AD的5xFAD小鼠模型中，从钙/钙调蛋白依赖蛋白激酶2A（CAMK2A）神经元中敲除HuD（HuD基因敲除小鼠，HuDcKO）会导致Aβ斑块显著减少，并减轻一些与AD相关的行为。鉴于AD缺乏有效的治疗方法，我们提出降低HuD水平或功能有助于减少Aβ斑块形成和与AD相关的病理变化。
