Discovery of a Highly Conserved Peptide in the Iron Transporter Melanotransferrin that Traverses an Intact Blood Brain Barrier and Localizes in Neural Cells.

Autor:	Singh CSB; Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada.; The Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, BC, Canada.; Centre for Blood Research, University of British Columbia, Vancouver, BC, Canada.; The Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada.; Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada., Eyford BA; Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada.; The Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, BC, Canada.; Centre for Blood Research, University of British Columbia, Vancouver, BC, Canada.; The Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada., Abraham T; Department of Neural and Behavioral Sciences and Microscopy Imaging Core Lab, Pennsylvania State College of Medicine, Hershey, PA, United States., Munro L; Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada.; The Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, BC, Canada.; Centre for Blood Research, University of British Columbia, Vancouver, BC, Canada.; The Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada., Choi KB; Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada.; The Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, BC, Canada.; Centre for Blood Research, University of British Columbia, Vancouver, BC, Canada.; The Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada., Okon M; Department of Chemistry, University of British Columbia, Vancouver, BC, Canada., Vitalis TZ; Bioasis Technologies Inc., Guilford, CT, United States., Gabathuler R; Bioasis Technologies Inc., Guilford, CT, United States.; King's College London, London, United Kingdom., Lu CJ; Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada.; The Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, BC, Canada.; Centre for Blood Research, University of British Columbia, Vancouver, BC, Canada.; The Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada., Pfeifer CG; Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada.; The Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, BC, Canada.; Centre for Blood Research, University of British Columbia, Vancouver, BC, Canada.; The Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada., Tian MM; Bioasis Technologies Inc., Guilford, CT, United States., Jefferies WA; Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada.; The Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, BC, Canada.; Centre for Blood Research, University of British Columbia, Vancouver, BC, Canada.; The Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada.; Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.; Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada.; Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada.; Department of Zoology, University of British Columbia, Vancouver, BC, Canada.
Jazyk:	angličtina
Zdroj:	Frontiers in neuroscience [Front Neurosci] 2021 Jun 02; Vol. 15, pp. 596976. Date of Electronic Publication: 2021 Jun 02 (Print Publication: 2021).
DOI:	10.3389/fnins.2021.596976
Abstrakt:	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. Competing Interests: Bioasis Technologies Inc., (BTI) is a University of British Columbia start-up company. TZV, RG, and MMT were employees and equity holders in BTI at the time this work was undertaken. WAJ was the founding scientist and an equity holder in BTI at the time this work was undertaken. The funding sources had no influence in the study design, data collection, analysis or interpretation of data, in the writing of the manuscript or on the decision to submit for publication. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Singh, Eyford, Abraham, Munro, Choi, Okon, Vitalis, Gabathuler, Lu, Pfeifer, Tian and Jefferies.)
Databáze:	MEDLINE
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