Regeneration in the central nervous system
Regeneration in the central nervous system
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DOI：
10.1016/s0531-5565(02)00165-1
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发表时间：
2003-01-01
影响因子：
3.9
通讯作者：
Bandtlow, CE
中科院分区：
文献类型：
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作者：
Bandtlow, CE
与新生儿轴突不同，哺乳动物成年中枢神经系统轴突在损伤后不能再生。这种再生能力的发育丧失与髓鞘形成的发生有关。同样，髓磷脂或髓磷脂相关成分，如Nogo-A和髓磷脂相关糖蛋白（MAG）抑制年老神经元的再生，而不是年轻神经元。鉴定导致再生能力发育丧失的分子事件对于制定促进成人损伤后再生的策略至关重要。内源性环核苷酸cAMP和cGMP水平被认为决定了神经元对各种轴突引导因子的反应性。cAMP浓度升高阻断Nogo-A或MAG诱导的老年神经元神经突生长抑制，而抑制年轻神经元cAMP水平使它们对Nogo-A和MAG敏感。有趣的是，cAMP水平升高消除了Nogo-A和MAG介导的成年神经元RhoA的激活和Rac1的下调。相反，cAMP升高导致RhoA失活，阻止下游效应蛋白的激活，而Rac被激活。因此，我们得出结论，内源性神经元cAMP水平通过调节rho GTPase活性来决定神经元对髓鞘相关神经突生长抑制剂的反应性。(C) 2002年Elsevier Science Inc.出版
Unlike neonatal axons, mammalian adult axons of the CNS do not regenerate after injury. This developmental loss of regenerative capacity, is correlated with the onset of myelination. Likewise, myelin, or myelin-associated components such as Nogo-A and myelin-associated glycoprotein (MAG) inhibit regeneration from older but not younger neurons. Identification of the molecular events responsible for this developmental loss of regenerative capacity is central to devise strategies to encourage regeneration in adults after injury. Endogenous levels of the cyclic nucleotides cAMP and cGMP have been suggested to determine the neuronal responsiveness to various axonal guidance factors. Elevating cAMP concentrations block Nogo-A or MAG induced inhibition of neurite outgrowth in older neurons, whereas suppressing cAMP levels in young neurons renders them susceptible to Nogo-A and MAG. Interestingly, elevated cAMP levels abrogated the Nogo-A and MAG mediated activation of RhoA and down regulation of Rac1 in adult neurons. In contrast, elevation of cAMP leads to the inactivation of RhoA and prevents activation of downstream effector proteins, while Rac is activated. We therefore conclude that the endogenous neuronal cAMP levels determine the neuronal responsiveness to myelin-associated neurite growth inhibitors by regulating rho GTPase activities. (C) 2002 Published by Elsevier Science Inc.