Singh Chaahat S B, Eyford Brett A, Abraham Thomas, Munro Lonna, Choi Kyung Bok, Okon Mark, Vitalis Timothy Z, Gabathuler Reinhard, Lu Chieh-Ju, Pfeifer Cheryl G, Tian Mei Mei, Jefferies Wilfred A
Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada.
The Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, BC, Canada.
Front Neurosci. 2021 Jun 2;15:596976. doi: 10.3389/fnins.2021.596976. eCollection 2021.
The blood-brain barrier (BBB) hinders the distribution of therapeutics intended for treatment of diseases of the brain. Our previous studies demonstrated that that a soluble form of melanotransferrin (MTf; Uniprot P08582; also known as p97, MFI2, and CD228), a mammalian iron-transport protein, is an effective carrier for delivery of drug conjugates across the BBB into the brain and was the first BBB targeting delivery system to demonstrate therapeutic efficacy within the brain. Here, we performed a screen to identify peptides from MTf capable of traversing the BBB. We identified a highly conserved 12-amino acid peptide, termed MTfp, that retains the ability to cross the intact BBB intact, distributes throughout the parenchyma, and enter endosomes and lysosomes within neurons, astrocytes and microglia in the brain. This peptide may provide a platform for the transport of therapeutics to the CNS, and thereby offers new avenues for potential treatments of neuropathologies that are currently refractory to existing therapies.
血脑屏障（BBB）阻碍了用于治疗脑部疾病的治疗药物的分布。我们之前的研究表明，可溶性形式的黑素转铁蛋白（MTf；通用蛋白质数据库编号P08582；也称为p97、MFI2和CD228），一种哺乳动物铁转运蛋白，是将药物偶联物跨血脑屏障递送至脑内的有效载体，并且是首个在脑内显示出治疗效果的血脑屏障靶向递送系统。在此，我们进行了一项筛选，以鉴定MTf中能够穿越血脑屏障的肽段。我们鉴定出了一种高度保守的12个氨基酸的肽，称为MTfp，它保留了完整穿越完整血脑屏障的能力，分布于整个脑实质，并进入脑内神经元、星形胶质细胞和小胶质细胞内的内体和溶酶体。这种肽可能为治疗药物向中枢神经系统的转运提供一个平台，从而为目前现有疗法难以治疗的神经病理学疾病提供新的潜在治疗途径。
