3xTG 阿尔茨海默病小鼠中海马乙酰转移酶 p300/CBP 相关因子（PCAF）依赖性的空间记忆缺陷随年龄增长而衰减。

Department of Psychology, Collaborative Neuroscience Program, University of Guelph, Guelph, Ontario N1G 2W1, Canada.

Department of Psychology, University of Toronto Mississauga, Mississauga, Ontario L5L 1C6, Canada.

Learn Mem. 2022 Feb 15;29(3):71-76. doi: 10.1101/lm.053536.121. Print 2022 Mar.

Histone acetylation, catalyzed by histone acetyltransferases, has emerged as a promising therapeutic strategy in Alzheimer's disease (AD). By longitudinally characterizing spatial memory at 3, 6, and 9 mo of age, we show that acute activation and inhibition of the histone acetyltransferase PCAF remediated memory impairments in 3xTG-AD mice in an age-related bidirectional manner. At 3 and 6 mo of age, PCAF activation ameliorated memory deficits. At 9 mo of age, PCAF activation had no effect on spatial memory, whereas PCAF inhibition improved memory deficits in females. This work reveals a complex potential therapeutic role for PCAF in AD, initially benefitting memory but becoming detrimental as the disease progresses.

组蛋白乙酰化由组蛋白乙酰转移酶催化，它已成为治疗阿尔茨海默病（AD）的一种有前途的策略。通过在 3、6 和 9 个月龄时纵向描述空间记忆，我们发现急性激活和抑制组蛋白乙酰转移酶 PCAF 以与年龄相关的双向方式改善了 3xTG-AD 小鼠的记忆障碍。在 3 和 6 个月龄时，PCAF 的激活改善了记忆缺陷。在 9 个月龄时，PCAF 的激活对空间记忆没有影响，而 PCAF 的抑制则改善了雌性动物的记忆缺陷。这项工作揭示了 PCAF 在 AD 中复杂的潜在治疗作用，最初对记忆有益，但随着疾病的进展，它变得有害。