Department of Morphology & Genetics, Universidade Federal de São Paulo (UNIFESP), São Paulo 04023-062, SP, Brazil.
Genes (Basel). 2023 Jan 29;14(2):347. doi: 10.3390/genes14020347.
Since Late-onset Alzheimer's disease (LOAD) derives from a combination of genetic variants and environmental factors, epigenetic modifications have been predicted to play a role in the etiopathology of LOAD. Along with DNA methylation, histone modifications have been proposed as the main epigenetic modifications that contribute to the pathologic mechanisms of LOAD; however, little is known about how these mechanisms contribute to the disease's onset or progression. In this review, we highlighted the main histone modifications and their functional role, including histone acetylation, histone methylation, and histone phosphorylation, as well as changes in such histone modifications that occur in the aging process and mainly in Alzheimer's disease (AD). Furthermore, we pointed out the main epigenetic drugs tested for AD treatment, such as those based on histone deacetylase (HDAC) inhibitors. Finally, we remarked on the perspectives around the use of such epigenetics drugs for treating AD.
由于晚发性阿尔茨海默病(LOAD)源于遗传变异和环境因素的综合作用,因此预测表观遗传修饰在 LOAD 的发病机制中发挥作用。除了 DNA 甲基化,组蛋白修饰也被认为是导致 LOAD 病理机制的主要表观遗传修饰;然而,对于这些机制如何导致疾病的发生或进展知之甚少。在这篇综述中,我们强调了主要的组蛋白修饰及其功能作用,包括组蛋白乙酰化、组蛋白甲基化和组蛋白磷酸化,以及在衰老过程中主要在阿尔茨海默病(AD)中发生的这些组蛋白修饰的变化。此外,我们还指出了针对 AD 治疗测试的主要表观遗传药物,如基于组蛋白去乙酰化酶(HDAC)抑制剂的药物。最后,我们提到了使用这些表观遗传学药物治疗 AD 的前景。