The Emerging Role of Epigenetics in Cerebral Ischemia

被引:48
作者
Hu, Zhiping [1 ]
Zhong, Bingwu [1 ,2 ]
Tan, Jieqiong [3 ]
Chen, Chunli [1 ]
Lei, Qiang [1 ]
Zeng, Liuwang [1 ]
机构
[1] Cent S Univ, Xiangya Hosp 2, Dept Neurol, Changsha 410011, Hunan, Peoples R China
[2] Cent S Univ, Xiangya Hosp 2, Dept Tradit Chinese Med, Changsha 410011, Hunan, Peoples R China
[3] Cent S Univ, Natl Key Lab Med Genet, Changsha 410078, Hunan, Peoples R China
基金
中国国家自然科学基金;
关键词
Cerebral ischemia; DNA methylation; Epigenetic mechanisms; Histone deacetylase; Histone methylation; miRNAs; NEURONAL CELL-DEATH; HISTONE DEACETYLASE INHIBITOR; OXYGEN-GLUCOSE DEPRIVATION; TRANSIENT FOCAL ISCHEMIA; DOWN-REGULATION; MICRORNA EXPRESSION; MOUSE-BRAIN; UP-REGULATION; ISCHEMIA/REPERFUSION INJURY; CIRCULATING MICRORNAS;
D O I
10.1007/s12035-016-9788-3
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Despite great progresses in the treatment and prevention of ischemic stroke, it is still among the leading causes of death and serious long-term disability all over the world, indicating that innovative neural regenerative and neuroprotective agents are urgently needed for the development of therapeutic approaches with greater efficacy for ischemic stroke. More and more evidence suggests that a spectrum of epigenetic processes play an important role in the pathophysiology of cerebral ischemia. In the present review, we first discuss recent developments in epigenetic mechanisms, especially their roles in the pathophysiology of cerebral ischemia. Specifically, we focus on DNA methylation, histone deacetylase, histone methylation, and microRNAs (miRNAs) in the regulation of vascular and neuronal regeneration after cerebral ischemia. Additionally, we highlight epigenetic strategies for ischemic stroke treatments, including the inhibition of histone deacetylase enzyme and DNA methyltransferase activities, and miRNAs. These therapeutic strategies are far from clinic use, but preliminary data indicate that neuroprotective agents targeting these pathways can modulate neural cell regeneration and promote brain repair and functional recovery after cerebral ischemia. A better understanding of how epigenetics influences the process and progress of cerebral ischemia will pave the way for discovering more sensitive and specific biomarkers and new targets and therapeutics for ischemic stroke.
引用
收藏
页码:1887 / 1905
页数:19
相关论文
共 173 条
[1]  
[Anonymous], 2014, SCI WORLD J, DOI DOI 10.1155/2014/562797
[2]  
[Anonymous], KNOWLEDGE BASED SYST, DOI DOI 10.1161/STR0KEAHA.112.664698
[3]  
[Anonymous], 2014, NEW J SCI, DOI DOI 10.1155/2014/756240
[4]   Blood Brain Barrier and Neuroinflammation Are Critical Targets of IGF-1-Mediated Neuroprotection in Stroke for Middle-Aged Female Rats [J].
Bake, Shameena ;
Selvamani, Amutha ;
Cherry, Jessica ;
Sohrabji, Farida .
PLOS ONE, 2014, 9 (03)
[5]   Histone deacetylase inhibitors preserve function in aging axons [J].
Baltan, Selva .
JOURNAL OF NEUROCHEMISTRY, 2012, 123 :108-115
[6]   Expression of Histone Deacetylases in Cellular Compartments of the Mouse Brain and the Effects of Ischemia [J].
Baltan, Selva ;
Bachleda, Amelia ;
Morrison, Richard S. ;
Murphy, Sean P. .
TRANSLATIONAL STROKE RESEARCH, 2011, 2 (03) :411-423
[7]   Histone Deacetylase Inhibitors Preserve White Matter Structure and Function during Ischemia by Conserving ATP and Reducing Excitotoxicity [J].
Baltan, Selva ;
Murphy, Sean P. ;
Danilov, Camelia A. ;
Bachleda, Amelia ;
Morrison, Richard S. .
JOURNAL OF NEUROSCIENCE, 2011, 31 (11) :3990-3999
[8]   Complement Protein C1q-Mediated Neuroprotection Is Correlated with Regulation of Neuronal Gene and MicroRNA Expression [J].
Benoit, Marie E. ;
Tenner, Andrea J. .
JOURNAL OF NEUROSCIENCE, 2011, 31 (09) :3459-3469
[9]   MicroRNAs participate in the murine oligodendroglial response to perinatal hypoxia-ischemia [J].
Birch, Derin ;
Britt, Blair C. ;
Dukes, Silena C. ;
Kessler, John A. ;
Dizon, Maria L. V. .
PEDIATRIC RESEARCH, 2014, 76 (04) :334-340
[10]   MicroRNA-21 protects neurons from ischemic death [J].
Buller, Ben ;
Liu, Xianshuang ;
Wang, Xinli ;
Zhang, Rui L. ;
Zhang, Li ;
Hozeska-Solgot, Ann ;
Chopp, Michael ;
Zhang, Zheng G. .
FEBS JOURNAL, 2010, 277 (20) :4299-4307