Discovery of a Highly Conserved Peptide in the Iron Transporter Melanotransferrin that Traverses an Intact Blood Brain Barrier and Localizes in Neural Cells
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...
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| Format: | Article |
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Frontiers Media S.A.
2021-06-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2021.596976/full |
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| author | Chaahat S. B. Singh Chaahat S. B. Singh Chaahat S. B. Singh Chaahat S. B. Singh Chaahat S. B. Singh Brett A. Eyford Brett A. Eyford Brett A. Eyford Brett A. Eyford Thomas Abraham Lonna Munro Lonna Munro Lonna Munro Lonna Munro Kyung Bok Choi Kyung Bok Choi Kyung Bok Choi Kyung Bok Choi Mark Okon Timothy Z. Vitalis Reinhard Gabathuler Reinhard Gabathuler Chieh-Ju Lu Chieh-Ju Lu Chieh-Ju Lu Chieh-Ju Lu Cheryl G. Pfeifer Cheryl G. Pfeifer Cheryl G. Pfeifer Cheryl G. Pfeifer Mei Mei Tian Wilfred A. Jefferies Wilfred A. Jefferies Wilfred A. Jefferies Wilfred A. Jefferies Wilfred A. Jefferies Wilfred A. Jefferies Wilfred A. Jefferies Wilfred A. Jefferies |
| author_facet | Chaahat S. B. Singh Chaahat S. B. Singh Chaahat S. B. Singh Chaahat S. B. Singh Chaahat S. B. Singh Brett A. Eyford Brett A. Eyford Brett A. Eyford Brett A. Eyford Thomas Abraham Lonna Munro Lonna Munro Lonna Munro Lonna Munro Kyung Bok Choi Kyung Bok Choi Kyung Bok Choi Kyung Bok Choi Mark Okon Timothy Z. Vitalis Reinhard Gabathuler Reinhard Gabathuler Chieh-Ju Lu Chieh-Ju Lu Chieh-Ju Lu Chieh-Ju Lu Cheryl G. Pfeifer Cheryl G. Pfeifer Cheryl G. Pfeifer Cheryl G. Pfeifer Mei Mei Tian Wilfred A. Jefferies Wilfred A. Jefferies Wilfred A. Jefferies Wilfred A. Jefferies Wilfred A. Jefferies Wilfred A. Jefferies Wilfred A. Jefferies Wilfred A. Jefferies |
| author_sort | Chaahat S. B. Singh |
| collection | DOAJ |
| description | 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 undigested, distribute 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. |
| first_indexed | 2024-12-14T18:02:59Z |
| format | Article |
| id | doaj.art-288f8666a28c48d19137c9e3c081e799 |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-12-14T18:02:59Z |
| publishDate | 2021-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-288f8666a28c48d19137c9e3c081e7992022-12-21T22:52:25ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2021-06-011510.3389/fnins.2021.596976596976Discovery of a Highly Conserved Peptide in the Iron Transporter Melanotransferrin that Traverses an Intact Blood Brain Barrier and Localizes in Neural CellsChaahat S. B. Singh0Chaahat S. B. Singh1Chaahat S. B. Singh2Chaahat S. B. Singh3Chaahat S. B. Singh4Brett A. Eyford5Brett A. Eyford6Brett A. Eyford7Brett A. Eyford8Thomas Abraham9Lonna Munro10Lonna Munro11Lonna Munro12Lonna Munro13Kyung Bok Choi14Kyung Bok Choi15Kyung Bok Choi16Kyung Bok Choi17Mark Okon18Timothy Z. Vitalis19Reinhard Gabathuler20Reinhard Gabathuler21Chieh-Ju Lu22Chieh-Ju Lu23Chieh-Ju Lu24Chieh-Ju Lu25Cheryl G. Pfeifer26Cheryl G. Pfeifer27Cheryl G. Pfeifer28Cheryl G. Pfeifer29Mei Mei Tian30Wilfred A. Jefferies31Wilfred A. Jefferies32Wilfred A. Jefferies33Wilfred A. Jefferies34Wilfred A. Jefferies35Wilfred A. Jefferies36Wilfred A. Jefferies37Wilfred A. Jefferies38Michael Smith Laboratories, University of British Columbia, Vancouver, BC, CanadaThe Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, BC, CanadaCentre for Blood Research, University of British Columbia, Vancouver, BC, CanadaThe Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, CanadaDepartment of Medical Genetics, University of British Columbia, Vancouver, BC, CanadaMichael Smith Laboratories, University of British Columbia, Vancouver, BC, CanadaThe Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, BC, CanadaCentre for Blood Research, University of British Columbia, Vancouver, BC, CanadaThe Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, CanadaDepartment of Neural and Behavioral Sciences and Microscopy Imaging Core Lab, Pennsylvania State College of Medicine, Hershey, PA, United StatesMichael Smith Laboratories, University of British Columbia, Vancouver, BC, CanadaThe Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, BC, CanadaCentre for Blood Research, University of British Columbia, Vancouver, BC, CanadaThe Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, CanadaMichael Smith Laboratories, University of British Columbia, Vancouver, BC, CanadaThe Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, BC, CanadaCentre for Blood Research, University of British Columbia, Vancouver, BC, CanadaThe Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, CanadaDepartment of Chemistry, University of British Columbia, Vancouver, BC, CanadaBioasis Technologies Inc., Guilford, CT, United StatesBioasis Technologies Inc., Guilford, CT, United StatesKing’s College London, London, United KingdomMichael Smith Laboratories, University of British Columbia, Vancouver, BC, CanadaThe Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, BC, CanadaCentre for Blood Research, University of British Columbia, Vancouver, BC, CanadaThe Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, CanadaMichael Smith Laboratories, University of British Columbia, Vancouver, BC, CanadaThe Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, BC, CanadaCentre for Blood Research, University of British Columbia, Vancouver, BC, CanadaThe Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, CanadaBioasis Technologies Inc., Guilford, CT, United StatesMichael Smith Laboratories, University of British Columbia, Vancouver, BC, CanadaThe Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, BC, CanadaCentre for Blood Research, University of British Columbia, Vancouver, BC, CanadaThe Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, CanadaDepartment of Medical Genetics, University of British Columbia, Vancouver, BC, Canada0Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada1Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada2Department of Zoology, University of British Columbia, Vancouver, BC, CanadaThe 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 undigested, distribute 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.https://www.frontiersin.org/articles/10.3389/fnins.2021.596976/fullblood-brain barrerMTfpdrug delivery and targetingpeptide transportneuronal targetingmicroglial targeting |
| spellingShingle | Chaahat S. B. Singh Chaahat S. B. Singh Chaahat S. B. Singh Chaahat S. B. Singh Chaahat S. B. Singh Brett A. Eyford Brett A. Eyford Brett A. Eyford Brett A. Eyford Thomas Abraham Lonna Munro Lonna Munro Lonna Munro Lonna Munro Kyung Bok Choi Kyung Bok Choi Kyung Bok Choi Kyung Bok Choi Mark Okon Timothy Z. Vitalis Reinhard Gabathuler Reinhard Gabathuler Chieh-Ju Lu Chieh-Ju Lu Chieh-Ju Lu Chieh-Ju Lu Cheryl G. Pfeifer Cheryl G. Pfeifer Cheryl G. Pfeifer Cheryl G. Pfeifer Mei Mei Tian Wilfred A. Jefferies Wilfred A. Jefferies Wilfred A. Jefferies Wilfred A. Jefferies Wilfred A. Jefferies Wilfred A. Jefferies Wilfred A. Jefferies Wilfred A. Jefferies Discovery of a Highly Conserved Peptide in the Iron Transporter Melanotransferrin that Traverses an Intact Blood Brain Barrier and Localizes in Neural Cells Frontiers in Neuroscience blood-brain barrer MTfp drug delivery and targeting peptide transport neuronal targeting microglial targeting |
| title | Discovery of a Highly Conserved Peptide in the Iron Transporter Melanotransferrin that Traverses an Intact Blood Brain Barrier and Localizes in Neural Cells |
| title_full | Discovery of a Highly Conserved Peptide in the Iron Transporter Melanotransferrin that Traverses an Intact Blood Brain Barrier and Localizes in Neural Cells |
| title_fullStr | Discovery of a Highly Conserved Peptide in the Iron Transporter Melanotransferrin that Traverses an Intact Blood Brain Barrier and Localizes in Neural Cells |
| title_full_unstemmed | Discovery of a Highly Conserved Peptide in the Iron Transporter Melanotransferrin that Traverses an Intact Blood Brain Barrier and Localizes in Neural Cells |
| title_short | Discovery of a Highly Conserved Peptide in the Iron Transporter Melanotransferrin that Traverses an Intact Blood Brain Barrier and Localizes in Neural Cells |
| title_sort | discovery of a highly conserved peptide in the iron transporter melanotransferrin that traverses an intact blood brain barrier and localizes in neural cells |
| topic | blood-brain barrer MTfp drug delivery and targeting peptide transport neuronal targeting microglial targeting |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2021.596976/full |
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