Instituto de Neurociencias, Av. Santiago Ramon y Cajal s/n. Sant Joan d'Alacant 03550, Alicante, Spain.
Curr Pharm Des. 2013;19(28):5051-64. doi: 10.2174/13816128113199990382.
Neuropsychiatric pathologies, including neurodegenerative diseases and neurodevelopmental syndromes, are frequently associated with dysregulation of various essential cellular mechanisms, such as transcription, mitochondrial respiration and protein degradation. In these complex scenarios, it is difficult to pinpoint the specific molecular dysfunction that initiated the pathology or that led to the fatal cascade of events that ends with the death of the neuron. Among the possible original factors, epigenetic dysregulation has attracted special attention. This review focuses on two highly related epigenetic factors that are directly involved in a number of neurological disorders, the lysine acetyltransferases CREB-binding protein (CBP) and E1A-associated protein p300 (p300). We first comment on the role of chromatin acetylation and the enzymes that control it, particularly CBP and p300, in neuronal plasticity and cognition. Next, we describe the involvement of these proteins in intellectual disability and in different neurodegenerative diseases. Finally, we discuss the potential of ameliorative strategies targeting CBP/p300 for the treatment of these disorders.
神经精神病理学，包括神经退行性疾病和神经发育综合征，常与各种重要细胞机制的失调有关，如转录、线粒体呼吸和蛋白质降解。在这些复杂的情况下，很难确定引发病理学的特定分子功能障碍，或者导致以神经元死亡为终点的致命级联事件的原因。在可能的原始因素中，表观遗传失调引起了特别关注。本篇综述专注于两种高度相关的表观遗传因子，它们直接涉及多种神经疾病，即赖氨酸乙酰转移酶 CREB 结合蛋白（CBP）和 E1A 相关蛋白 p300（p300）。我们首先评论组蛋白乙酰化及其调控酶，特别是 CBP 和 p300，在神经元可塑性和认知中的作用。接下来，我们描述了这些蛋白在智力障碍和不同神经退行性疾病中的作用。最后，我们讨论了针对 CBP/p300 的改善策略在治疗这些疾病方面的潜力。
