Laboratory of Molecular Neuropathology, Jiangsu Key Laboratory of Neuropsychiatric Diseases & Department of Pharmacology, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China.
Int J Mol Sci. 2020 Sep 29;21(19):7182. doi: 10.3390/ijms21197182.
Parkinson's disease (PD) is one of the most common neurodegenerative disorders. The neuropathological features of PD are selective and progressive loss of dopaminergic neurons in the substantia nigra pars compacta, deficiencies in striatal dopamine levels, and the presence of intracellular Lewy bodies. Interactions among aging and genetic and environmental factors are considered to underlie the common etiology of PD, which involves multiple changes in cellular processes. Recent studies suggest that changes in lysine acetylation and deacetylation of many proteins, including histones and nonhistone proteins, might be tightly associated with PD pathogenesis. Here, we summarize the changes in lysine acetylation of both histones and nonhistone proteins, as well as the related lysine acetyltransferases (KATs) and lysine deacetylases (KDACs), in PD patients and various PD models. We discuss the potential roles and underlying mechanisms of these changes in PD and highlight that restoring the balance of lysine acetylation/deacetylation of histones and nonhistone proteins is critical for PD treatment. Finally, we discuss the advantages and disadvantages of different KAT/KDAC inhibitors or activators in the treatment of PD models and emphasize that SIRT1 and SIRT3 activators and SIRT2 inhibitors are the most promising effective therapeutics for PD.
帕金森病（PD）是最常见的神经退行性疾病之一。PD 的神经病理学特征是黑质致密部多巴胺能神经元选择性和进行性丧失、纹状体多巴胺水平降低以及细胞内路易体的存在。衰老以及遗传和环境因素之间的相互作用被认为是 PD 的共同病因基础，涉及细胞过程的多种变化。最近的研究表明，许多蛋白质（包括组蛋白和非组蛋白）赖氨酸乙酰化和去乙酰化的变化可能与 PD 的发病机制密切相关。在这里，我们总结了 PD 患者和各种 PD 模型中组蛋白和非组蛋白蛋白质赖氨酸乙酰化的变化，以及相关的赖氨酸乙酰转移酶（KAT）和赖氨酸去乙酰化酶（KDAC）。我们讨论了这些变化在 PD 中的潜在作用和潜在机制，并强调恢复组蛋白和非组蛋白蛋白质赖氨酸乙酰化/去乙酰化的平衡对于 PD 治疗至关重要。最后，我们讨论了不同 KAT/KDAC 抑制剂或激活剂在 PD 模型治疗中的优缺点，并强调 SIRT1 和 SIRT3 激活剂和 SIRT2 抑制剂是 PD 最有前途的有效治疗方法。
