Verrillo Lucia, Di Palma Rosita, de Bellis Alberto, Drongitis Denise, Miano Maria Giuseppina
Institute of Genetics and Biophysics Adriano Buzzati-Traverso, CNR, 80131 Naples, Italy.
A.O.R.N. S. Anna and S. Sebastiano Hospital, Division of Neurosurgery, 81100 Caserta, Italy.
Biomolecules. 2023 Aug 24;13(9):1301. doi: 10.3390/biom13091301.
Neuroplasticity is a crucial property of the central nervous system to change its activity in response to intrinsic or extrinsic stimuli. This is mainly achieved through the promotion of changes in the epigenome. One of the epi-drivers priming this process is suberoylanilide hydroxamic acid (SAHA or Vorinostat), a pan-histone deacetylase inhibitor that modulates and promotes neuroplasticity in healthy and disease conditions. Knowledge of the specific molecular changes induced by this epidrug is an important area of neuro-epigenetics for the identification of new compounds to treat cognition impairment and/or epilepsy. In this review, we summarize the findings obtained in cellular and animal models of various brain disorders, highlighting the multiple mechanisms activated by SAHA, such as improvement of memory, learning and behavior, and correction of faulty neuronal functioning. Supporting this evidence, and data underline how SAHA positively regulates the expression of neuronal genes and microtubule dynamics, induces neurite outgrowth and spine density, and enhances synaptic transmission and potentiation. In particular, we outline studies regarding neurodevelopmental disorders with pharmaco-resistant seizures and/or severe cognitive impairment that to date lack effective drug treatments in which SAHA could ameliorate defective neuroplasticity.
神经可塑性是中枢神经系统的一项关键特性，它能够响应内在或外在刺激而改变其活动。这主要是通过促进表观基因组的变化来实现的。启动这一过程的表观驱动因素之一是辛二酰苯胺异羟肟酸（SAHA或伏立诺他），一种泛组蛋白去乙酰化酶抑制剂，在健康和疾病状态下调节并促进神经可塑性。了解这种表观药物诱导的特定分子变化，是神经表观遗传学领域的一个重要方面，有助于识别治疗认知障碍和/或癫痫的新化合物。在这篇综述中，我们总结了在各种脑部疾病的细胞和动物模型中获得的研究结果，强调了SAHA激活的多种机制，如改善记忆、学习和行为，以及纠正有缺陷的神经元功能。支持这一证据的数据强调了SAHA如何正向调节神经元基因的表达和微管动力学，诱导神经突生长和树突棘密度，并增强突触传递和突触增强。特别是，我们概述了关于药物难治性癫痫和/或严重认知障碍的神经发育障碍的研究，这些疾病迄今为止缺乏有效的药物治疗，而SAHA可以改善有缺陷的神经可塑性。
