The Mitogen-Activated Protein Kinase (MAPK) Signaling Pathway as a Discovery Target in Stroke

被引:207
作者
Sun, Jing [1 ]
Nan, Guangxian [1 ]
机构
[1] Jilin Univ, China Japan Union Hosp, Dept Neurol, 126 Xiantai St, Changchun 130000, Jilin, Peoples R China
关键词
MAPK pathway; Stroke; Inflammation; Apoptosis; BLOOD-BRAIN-BARRIER; EXPERIMENTAL SUBARACHNOID HEMORRHAGE; NECROSIS-FACTOR-ALPHA; ATTENUATES CEREBRAL VASOSPASM; N-TERMINAL KINASE; INTRACEREBRAL HEMORRHAGE; TNF-ALPHA; P38; MAPK; CONTRACTILE RECEPTORS; INFLAMMATORY INJURY;
D O I
10.1007/s12031-016-0717-8
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Protein kinases are critical modulators of a variety of intracellular and extracellular signal transduction pathways, and abnormal phosphorylation events can contribute to disease progression in a variety of diseases. As a result, protein kinases have emerged as important new drug targets for small molecule therapeutics. The mitogen-activated protein kinase (MAPK) signaling pathway transmits signals from the cell membrane to the nucleus in response to a variety of different stimuli. Because this pathway controls a broad spectrum of cellular processes, including growth, inflammation, and stress responses, it is accepted as a therapeutic target for cancer and peripheral inflammatory disorders. There is also increasing evidence that MAPK is an important regulator of ischemic and hemorrhagic cerebral vascular disease, raising the possibility that it might be a drug discovery target for stroke. In this review, we discuss the MAPK signaling pathway in association with its activation in stroke-induced brain injury.
引用
收藏
页码:90 / 98
页数:9
相关论文
共 67 条
[1]   Human cerebrovascular contractile receptors are upregulated via a B-Raf/MEK/ERK-sensitive signaling pathway [J].
Ahnstedt, Hilda ;
Saveland, Hans ;
Nilsson, Ola ;
Edvinsson, Lars .
BMC NEUROSCIENCE, 2011, 12
[2]   Secretion of matrix metalloproteinase-9 by the proinflammatory cytokine, IL-1β:: a role for the dual signalling pathways, Akt and Erk [J].
Amin, ARMR ;
Senga, T ;
Oo, ML ;
Thant, AA ;
Hamaguchi, M .
GENES TO CELLS, 2003, 8 (06) :515-523
[3]   Inhibition of cerebrovascular raf activation attenuates cerebral blood flow and prevents upregulation of contractile receptors after subarachnoid hemorrhage [J].
Ansar, Saema ;
Maddahi, Aida ;
Edvinsson, Lars .
BMC NEUROSCIENCE, 2011, 12
[4]   Molecular Pathophysiology of Cerebral Hemorrhage Secondary Brain Injury [J].
Aronowski, Jaroslaw ;
Zhao, Xiurong .
STROKE, 2011, 42 (06) :1781-1786
[5]   Thrombin and hemin as central factors in the mechanisms of intracerebral hemorrhage-induced secondary brain injury and as potential targets for intervention [J].
Babu, Ranjith ;
Bagley, Jacob H. ;
Di, Chunhui ;
Friedm, Allan H. ;
Adamson, Cory .
NEUROSURGICAL FOCUS, 2012, 32 (04)
[6]   Spinal release of tumour necrosis factor activates c-Jun N-terminal kinase and mediates inflammation-induced hypersensitivity [J].
Bas, D. B. ;
Abdelmoaty, S. ;
Sandor, K. ;
Codeluppi, S. ;
Fitzsimmons, B. ;
Steinauer, J. ;
Hua, X. Y. ;
Yaksh, T. L. ;
Svensson, C. I. .
EUROPEAN JOURNAL OF PAIN, 2015, 19 (02) :260-270
[7]   ERK1/2 inhibition attenuates cerebral blood flow reduction and abolishes ETB and 5-HT1B receptor upregulation after subarachnoid hemorrhage in rat [J].
Beg, Saema A. S. ;
Hansen-Schwartz, Jacob A. ;
Vikman, Petter J. ;
Xu, Cang-Bao ;
Edvinsson, Lars I. H. .
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 2006, 26 (06) :846-856
[8]   The p38α mitogen-activated protein kinase as a central nervous system drug discovery target [J].
Borders, Aaron S. ;
de Almeida, Lucia ;
Van Eldik, Linda J. ;
Watterson, Martin .
BMC NEUROSCIENCE, 2008, 9 (Suppl 2)
[9]   Activated Microglia Are Less Vulnerable to Hemin Toxicity due to Nitric Oxide-Dependent Inhibition of JNK and p38 MAPK Activation [J].
Cai, Ying ;
Cho, Geum-Sil ;
Ju, Chung ;
Wang, Si-Ling ;
Ryu, Jong Hoon ;
Shin, Chan Young ;
Kim, Hee-Sun ;
Nam, Kung-Woo ;
Jalin, Angela M. A. Anthony ;
Sun, Woong ;
Choi, In-Young ;
Kim, Won-Ki .
JOURNAL OF IMMUNOLOGY, 2011, 187 (03) :1314-1321
[10]   Looking at the blood-brain barrier: Molecular anatomy and possible investigation approaches [J].
Cardoso, Filipa Lourenco ;
Brites, Dora ;
Brito, Maria Alexandra .
BRAIN RESEARCH REVIEWS, 2010, 64 (02) :328-363