Neuroprotective versus tumorigenic protein kinase C activators

被引:75
作者
Nelson, T. J. [1 ]
Alkon, D. L. [1 ]
机构
[1] W Virginia Univ, Sch Med, Blanchette Rockefeller Neurosci Inst, Morgantown, WV 26506 USA
关键词
AMYLOID PRECURSOR PROTEIN; PHORBOL ESTER; ALZHEIMERS-DISEASE; BINDING DOMAIN; SPATIAL MEMORY; CELL-DEATH; SIGNALING COMPLEX; CONVERTING-ENZYME; MEMBRANE-BINDING; TUMOR PROMOTERS;
D O I
10.1016/j.tibs.2008.11.006
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 kinase C (PKC) activators possess potent neurotrophic and neuroprotective activity, thus indicating potential applications in treating neurodegenerative diseases, stroke and traumatic brain injury. Although some activators, such as bryostatin and gnidimacrin, have been tested as antitumor agents, others, such as phorbol esters, are potent tumor promoters. All PKC activators downregulate PKC at high concentrations and long application times. However, tumorigenic activators downregulate certain PKC isozymes, especially PKC delta, more strongly. Tumorigenic activators possess unique structural features that could account for this difference. At concentrations that minimize PKC downregulation, PKC activators can improve long-term memory, reduce beta-amyloid levels, induce synaptogenesis, promote neuronal repair and inhibit cell proliferation. Intermittent, low concentrations of structurally specific, non-tumorigenic PKC activators, therefore, could offer therapeutic benefit for a variety of neurologic disorders.
引用
收藏
页码:136 / 145
页数:10
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