Discovery of a Highly Conserved Peptide in the Iron Transporter Melanotransferrin that Traverses an Intact Blood Brain Barrier and Localizes in Neural Cells
| Autor: | Chaahat S. B. Singh, Brett A. Eyford, Thomas Abraham, Lonna Munro, Kyung Bok Choi, Mark Okon, Timothy Z. Vitalis, Reinhard Gabathuler, Chieh-Ju Lu, Cheryl G. Pfeifer, Mei Mei Tian, Wilfred A. Jefferies |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Endosome
Peptide Neurosciences. Biological psychiatry. Neuropsychiatry blood-brain barrer Blood–brain barrier MTfp microglial targeting 03 medical and health sciences 0302 clinical medicine glial targeting melanotransferrin Parenchyma medicine neuronal targeting 030304 developmental biology Original Research chemistry.chemical_classification 0303 health sciences Microglia General Neuroscience Transporter peptide transport drug delivery and targeting 3. Good health Cell biology medicine.anatomical_structure chemistry nervous system Peptide transport Melanotransferrin 030217 neurology & neurosurgery RC321-571 Neuroscience |
| Zdroj: | Frontiers in Neuroscience Frontiers in Neuroscience, Vol 15 (2021) |
| ISSN: | 1662-4548 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|