Beta secretase activity in peripheral nerve regeneration.
Beta secretase activity in peripheral nerve regeneration.
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DOI：
10.4103/1673-5374.217319
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发表时间：
2017-10
影响因子：
6.1
通讯作者：
Farah MH
中科院分区：
文献类型：
--
作者：
Tallon C;Farah MH
虽然周围神经系统在神经损伤后具有再生能力，但其速度往往很慢，恢复效果不理想，导致患者功能下降。多年来，许多再生相关基因已经被鉴定出来，这可能会让我们对如何操纵这种内在的再生能力来增强周围神经损伤后的修复有一些了解。我们的实验室已经确定了膜结合蛋白酶-位点淀粉样蛋白前体蛋白切割酶1 (BACE1)，或β分泌酶，作为周围神经再生的潜在负调节因子。当-分泌酶活性水平在小鼠中通过零突变被废除时，坐骨神经挤压损伤后外周再生得到增强。相反，在小鼠中，当β分泌酶的过度表达使活性水平大大增加时，坐骨神经挤压损伤后神经再生和功能恢复受到损害。除了我们的工作，许多β分泌酶的底物被发现参与调节神经突的生长，有些甚至被确定为再生相关基因。在这篇综述中，我们开始讨论BACE1及其底物与轴突再生的关系，并推测利用BACE1抑制剂增强急性神经损伤后再生的可能性，以及在周围神经病变中的潜在应用。
While the peripheral nervous system has the capacity to regenerate following a nerve injury, it is often at a slow rate and results in unsatisfactory recovery, leaving patients with reduced function. Many regeneration associated genes have been identified over the years, which may shed some insight into how we can manipulate this intrinsic regenerative ability to enhance repair following peripheral nerve injuries. Our lab has identified the membrane bound protease beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1), or beta secretase, as a potential negative regulator of peripheral nerve regeneration. When beta secretase activity levels are abolished via a null mutation in mice, peripheral regeneration is enhanced following a sciatic nerve crush injury. Conversely, when activity levels are greatly increased by overexpressing beta secretase in mice, nerve regeneration and functional recovery are impaired after a sciatic nerve crush injury. In addition to our work, many substrates of beta secretase have been found to be involved in regulating neurite outgrowth and some have even been identified as regeneration associated genes. In this review, we set out to discuss BACE1 and its substrates with respect to axonal regeneration and speculate on the possibility of utilizing BACE1 inhibitors to enhance regeneration following acute nerve injury and potential uses in peripheral neuropathies.
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影响因子：
5.3
作者：
Fischer, LR;Culver, DG;Glass, JD
通讯作者：
Glass, JD
影响因子：
5.3
作者：
GEORGE, R;GRIFFIN, JW
通讯作者：
GRIFFIN, JW
影响因子：
4
作者：
Cebers, Gvido;Alexander, Robert C.;Kugler, Alan R.
通讯作者：
Kugler, Alan R.
DOI：
10.1083/jcb.149.7.1443
发表时间：
2000-06-26
期刊：
The Journal of cell biology
影响因子：
--
作者：
Frey D;Laux T;Xu L;Schneider C;Caroni P
通讯作者：
Caroni P
DOI：
10.1523/jneurosci.3708-08.2008
发表时间：
2008-10-29
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Ferguson AR;Christensen RN;Gensel JC;Miller BA;Sun F;Beattie EC;Bresnahan JC;Beattie MS
通讯作者：
Beattie MS