Tau Proteins Cross the Blood-Brain Barrier
Tau Proteins Cross the Blood-Brain Barrier
复制标题
DOI：
10.3233/jad-160542
复制
发表时间：
2017-01-01
影响因子：
4
通讯作者：
Zhang, Jing
中科院分区：
文献类型：
--
作者：
Banks, William A.;Kovac, Andrej;Zhang, Jing
牛头病变是许多神经退行性疾病的标志，包括阿尔茨海默病和创伤性脑损伤。已经证明淀粉样肽，α -突触核蛋白和朊蛋白穿过血脑屏障（BBB），有助于它们诱导疾病的能力。对于tau蛋白是否能穿过血脑屏障，我们知之甚少。在这里，我们系统地表征了几种关键形式的tau蛋白穿过血脑屏障，包括tau -441 (2N4R), tau -410 (2N3R)，截断的tau 151-391 （0N4R）和截断的tau 121-227。所有这些tau蛋白都很容易双向穿过血脑屏障；然而，只有Tau-410在其流入中含有饱和成分。tau蛋白在注射到大脑后也会进入血液，其中tau 121-227从大脑中退出的速度最慢。tau蛋白在脑和血液中的酶稳定性以及外周药代动力学方面有所不同。这些结果表明血源性tau蛋白可能导致脑部病变。该结果还表明，中枢神经系统可以影响血液中tau蛋白的水平，这提高了血液中tau蛋白水平可以作为中枢神经系统疾病生物标志物的可能性，正如其他错误折叠蛋白所表明的那样。
Tauopathies are a hallmark of many neurodegenerative diseases, including Alzheimer's disease and traumatic brain injuries. It has been demonstrated that amyloid-beta peptides, alpha-synuclein, and prion proteins cross the blood-brain barrier (BBB), contributing to their abilities to induce disease. Very little is known about whether tau proteins can cross the BBB. Here we systematically characterized several key forms of tau proteins to cross the BBB, including Tau-441 (2N4R), Tau-410 (2N3R), truncated tau 151-391 (0N4R), and truncated tau 121-227. All of these tau proteins crossed the BBB readily and bidirectonally; however, only Tau-410 had a saturable component to its influx. The tau proteins also entered the blood after their injection into the brain, with Tau 121-227 having the slowest exit from brain. The tau proteins varied in regards to their enzymatic stability in brain and blood and in their peripheral pharmacokinetics. These results show that blood-borne tau proteins could contribute to brain tauopathies. The result also suggest that the CNS can contribute to blood levels of tau, raising the possibility that, as suggested for other misfolded proteins, blood levels of tau proteins could be used as a biomarker of CNS disease.