Imbalance of Lysine Acetylation Contributes to the Pathogenesis of Parkinson's Disease.
Imbalance of Lysine Acetylation Contributes to the Pathogenesis of Parkinson's Disease.
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赖氨酸乙酰化失衡导致帕金森病的发病机制
DOI：
10.3390/ijms21197182
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发表时间：
2020-09-29
影响因子：
5.6
通讯作者：
Ren H
中科院分区：
文献类型：
--
作者：
Wang R;Sun H;Wang G;Ren H
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丘脑部多巴胺能神经元的选择性和进行性损失、纹状体多巴胺水平的不足和细胞内路易体的存在。衰老与遗传和环境因素之间的相互作用被认为是PD的常见病因学的基础，其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的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，我们总结了组蛋白和非组蛋白的赖氨酸乙酰化的变化，以及相关的赖氨酸乙酰转移酶（KAT）和赖氨酸脱乙酰酶（KDAC），在PD患者和各种PD模型。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的赖氨酸乙酰化/脱乙酰化的平衡对PD治疗至关重要。最后，我们讨论了不同的KAT/KDAC抑制剂或激活剂在治疗PD模型中的优缺点，并强调SIRT 1和SIRT 3激活剂以及SIRT 2抑制剂是最有希望的有效治疗PD的药物。
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.
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影响因子：
9.8
作者：
de Oliveira RM;Vicente Miranda H;Francelle L;Pinho R;Szegö ÉM;Martinho R;Munari F;Lázaro DF;Moniot S;Guerreiro P;Fonseca-Ornelas L;Marijanovic Z;Antas P;Gerhardt E;Enguita FJ;Fauvet B;Penque D;Pais TF;Tong Q;Becker S;Kügler S;Lashuel HA;Steegborn C;Zweckstetter M;Outeiro TF
通讯作者：
Outeiro TF
帕金森氏病的遗传结构。
DOI：
10.1016/s1474-4422(19)30287-x
发表时间：
2020-02
期刊：
The Lancet. Neurology
影响因子：
--
作者：
Blauwendraat C;Nalls MA;Singleton AB
通讯作者：
Singleton AB
影响因子：
16
作者：
Fan, Jun;Shan, Changliang;Kang, Hee-Bum;Elf, Shannon;Xie, Jianxin;Tucker, Meghan;Gu, Ting-Lei;Aguiar, Mike;Lonning, Scott;Chen, Huaibin;Mohammadi, Moosa;Britton, Laura-Mae P.;Garcia, Benjamin A.;Aleckovic, Masa;Kang, Yibin;Kaluz, Stefan;Devi, Nara;Van Meir, Erwin G.;Hitosugi, Taro;Seo, Jae Ho;Lonial, Sagar;Gaddh, Manila;Arellano, Martha;Khoury, Hanna J.;Khuri, Fadlo R.;Boggon, Titus J.;Kang, Sumin;Chen, Jing
通讯作者：
Chen, Jing
DOI：
10.1073/pnas.51.5.786
发表时间：
1964-01-01
影响因子：
11.1
作者：
ALLFREY, VG;FAULKNER, R;MIRSKY, AE
通讯作者：
MIRSKY, AE
影响因子：
29
作者：
Anderson KA;Huynh FK;Fisher-Wellman K;Stuart JD;Peterson BS;Douros JD;Wagner GR;Thompson JW;Madsen AS;Green MF;Sivley RM;Ilkayeva OR;Stevens RD;Backos DS;Capra JA;Olsen CA;Campbell JE;Muoio DM;Grimsrud PA;Hirschey MD
通讯作者：
Hirschey MD