Melatonin Supplementation, a Strategy to Prevent Neurological Diseases through Maintaining Integrity of Blood Brain Barrier in Old People.
Melatonin Supplementation, a Strategy to Prevent Neurological Diseases through Maintaining Integrity of Blood Brain Barrier in Old People.
复制标题
补充褪黑激素，通过维持老年人血脑屏障的完整性来预防神经系统疾病的策略。
DOI：
10.3389/fnagi.2017.00165
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发表时间：
2017
影响因子：
4.8
通讯作者：
Jin X
中科院分区：
文献类型：
--
作者：
Liu WC;Wang X;Zhang X;Chen X;Jin X
血脑屏障（BBB）在维持中枢神经系统（CNS）神经功能所必需的微环境稳态中起着至关重要的作用。在面对各种外在或内在刺激时，血脑屏障（BBB）受损是老年人各种神经系统疾病（包括急、慢性脑缺血、阿尔茨海默病等）发病的早期事件，维持BBB完整性的治疗可以预防各种刺激引起的神经系统疾病。老年人常面临脓毒症的常见应激，在此期间，脂多糖（LPS）被释放到循环中，并破坏BBB的完整性。值得注意的是，在老年人和动物中存在褪黑激素水平的显著降低。褪黑激素已被证明通过多种途径保持BBB的完整性和渗透性：抑制基质金属蛋白酶-9（MMP-9），抑制NADPH氧化酶-2，以及影响沉默信息调节因子1（SIRT 1）和核苷酸结合寡聚化结构域样受体家族含pyrin结构域3（NLRP 3）炎性体。更重要的是，最近的一项研究表明，补充褪黑激素通过激活AMP活化蛋白激酶（AMPK）和抑制gp 91 phox来减轻LPS诱导的老年小鼠BBB损伤，这表明补充褪黑激素可能有助于通过维持老年人BBB的完整性来预防神经系统疾病。
Blood brain barrier (BBB) plays a crucial role in maintaining homeostasis of microenvironment that is essential to neural function of the central nervous system (CNS). When facing various extrinsic or intrinsic stimuli, BBB is damaged which is an early event in pathogenesis of a variety of neurological diseases in old patients including acute and chronic cerebral ischemia, Alzheimer’s disease and etc. Treatments that could maintain the integrity of BBB may prevent neurological diseases following various stimuli. Old people often face a common stress of sepsis, during which lipopolysaccharide (LPS) is released into circulation and the integrity of BBB is damaged. Of note, there is a significant decrease of melatonin level in old people and animal. Melatonin has been shown to preserves BBB integrity and permeability via a variety of pathways: inhibition of matrix metalloproteinase-9 (MMP-9), inhibition of NADPH oxidase-2, and impact on silent information regulator 1 (SIRT1) and nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome. More important, a recent study showed that melatonin supplementation alleviates LPS-induced BBB damage in old mice through activating AMP-activated protein kinase (AMPK) and inhibiting gp91phox, suggesting that melatonin supplementation may help prevent neurological diseases through maintaining the integrity of BBB in old people.