Apolipoprotein E-derived peptides reduce CNS inflammation: implications for therapy of neurological disease
Apolipoprotein E-derived peptides reduce CNS inflammation: implications for therapy of neurological disease
复制标题
DOI：
10.1111/j.1600-0404.2006.00680.x
复制
发表时间：
2006-01-01
影响因子：
3.5
通讯作者：
Vitek, M. P.
中科院分区：
文献类型：
--
作者：
Laskowitz, D. T.;Fillit, H.;Vitek, M. P.
载脂蛋白E4亚型(ApoE4)最初被认为是阿尔茨海默病的易感基因，最近也被认为与急性创伤和缺血性脑损伤后的不良预后有关。载脂蛋白E可能影响急慢性神经系统疾病预后的一个机制是通过下调神经胶质细胞激活和神经炎性反应。由于apoE全蛋白不容易通过血脑屏障(BBB)，其治疗潜力有限。然而，从apoE受体结合区衍生的较小的多肽已经被开发出来，以模拟完整apoE蛋白的抗炎和神经保护作用。这些apoE衍生的治疗多肽可以穿过血脑屏障，并已被证明可以改善小鼠脑损伤模型的功能和组织学结果。因此，apoE衍生多肽的开发代表了治疗急慢性神经系统疾病的一种新的治疗策略。
The apolipoprotein E4 isoform (apoE4) was initially identified as a susceptibility gene for the development of Alzheimer's disease, and has also recently been associated with poor outcome after acute traumatic and ischemic brain injury. One mechanism by which apoE may influence outcome in acute and chronic neurological disease is by downregulating glial activation and the neuroinflammatory response. Because it does not readily cross the blood-brain barrier (BBB), the apoE holoprotein has limited therapeutic potential. However, smaller peptides derived from the receptor binding region of apoE have been developed that mimic the functional anti-inflammatory and neuroprotective effects of the intact apoE protein. These apoE-derived therapeutic peptides cross the BBB and have been demonstrated to improve functional and histological outcomes in murine models of brain injury. Thus, the development of apoE-derived peptides represent a novel therapeutic strategy for the treatment of acute and chronic neurological disease.