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Discovery of a Highly Conserved Peptide in the Iron Transporter Melanotransferrin that Traverses an Intact Blood Brain Barrier and Localizes in Neural Cells.
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.
Afiliação
  • Singh CSB; Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada.
  • Eyford BA; The Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, BC, Canada.
  • Abraham T; Centre for Blood Research, University of British Columbia, Vancouver, BC, Canada.
  • Munro L; The Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada.
  • Choi KB; Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.
  • Okon M; Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada.
  • Vitalis TZ; The Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, BC, Canada.
  • Gabathuler R; Centre for Blood Research, University of British Columbia, Vancouver, BC, Canada.
  • Lu CJ; The Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada.
  • Pfeifer CG; Department of Neural and Behavioral Sciences and Microscopy Imaging Core Lab, Pennsylvania State College of Medicine, Hershey, PA, United States.
  • Tian MM; Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada.
  • Jefferies WA; The Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, BC, Canada.
Front Neurosci ; 15: 596976, 2021.
Article em En | MEDLINE | ID: mdl-34149342
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.
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Texto completo: 1 Base de dados: MEDLINE Idioma: En Revista: Front Neurosci Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Canadá

Texto completo: 1 Base de dados: MEDLINE Idioma: En Revista: Front Neurosci Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Canadá