Frontiers in Neuroscience (Jun 2021)
Discovery of a Highly Conserved Peptide in the Iron Transporter Melanotransferrin that Traverses an Intact Blood Brain Barrier and Localizes in Neural Cells
- 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
Affiliations
- Chaahat S. B. Singh
- Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada
- Chaahat S. B. Singh
- The Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, BC, Canada
- Chaahat S. B. Singh
- Centre for Blood Research, University of British Columbia, Vancouver, BC, Canada
- Chaahat S. B. Singh
- The Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada
- Chaahat S. B. Singh
- Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada
- Brett A. Eyford
- Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada
- Brett A. Eyford
- The Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, BC, Canada
- Brett A. Eyford
- Centre for Blood Research, University of British Columbia, Vancouver, BC, Canada
- Brett A. Eyford
- The Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada
- Thomas Abraham
- Department of Neural and Behavioral Sciences and Microscopy Imaging Core Lab, Pennsylvania State College of Medicine, Hershey, PA, United States
- Lonna Munro
- Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada
- Lonna Munro
- The Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, BC, Canada
- Lonna Munro
- Centre for Blood Research, University of British Columbia, Vancouver, BC, Canada
- Lonna Munro
- The Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada
- Kyung Bok Choi
- Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada
- Kyung Bok Choi
- The Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, BC, Canada
- Kyung Bok Choi
- Centre for Blood Research, University of British Columbia, Vancouver, BC, Canada
- Kyung Bok Choi
- The Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada
- Mark Okon
- Department of Chemistry, University of British Columbia, Vancouver, BC, Canada
- Timothy Z. Vitalis
- Bioasis Technologies Inc., Guilford, CT, United States
- Reinhard Gabathuler
- Bioasis Technologies Inc., Guilford, CT, United States
- Reinhard Gabathuler
- King’s College London, London, United Kingdom
- Chieh-Ju Lu
- Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada
- Chieh-Ju Lu
- The Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, BC, Canada
- Chieh-Ju Lu
- Centre for Blood Research, University of British Columbia, Vancouver, BC, Canada
- Chieh-Ju Lu
- The Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada
- Cheryl G. Pfeifer
- Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada
- Cheryl G. Pfeifer
- The Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, BC, Canada
- Cheryl G. Pfeifer
- Centre for Blood Research, University of British Columbia, Vancouver, BC, Canada
- Cheryl G. Pfeifer
- The Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada
- Mei Mei Tian
- Bioasis Technologies Inc., Guilford, CT, United States
- Wilfred A. Jefferies
- Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada
- Wilfred A. Jefferies
- The Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, BC, Canada
- Wilfred A. Jefferies
- Centre for Blood Research, University of British Columbia, Vancouver, BC, Canada
- Wilfred A. Jefferies
- The Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada
- Wilfred A. Jefferies
- Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada
- Wilfred A. Jefferies
- 0Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada
- Wilfred A. Jefferies
- 1Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada
- Wilfred A. Jefferies
- 2Department of Zoology, University of British Columbia, Vancouver, BC, Canada
- DOI
- https://doi.org/10.3389/fnins.2021.596976
- Journal volume & issue
-
Vol. 15
Abstract
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.
Keywords
- blood-brain barrer
- MTfp
- drug delivery and targeting
- peptide transport
- neuronal targeting
- microglial targeting