scholarly journals Comparison of Blood-Brain Barrier Transport of Glial-Derived Neurotrophic Factor (GDNF) and an IgG-GDNF Fusion Protein in the Rhesus Monkey

2009 ◽  
Vol 37 (12) ◽  
pp. 2299-2304 ◽  
Author(s):  
Ruben J. Boado ◽  
William M. Pardridge
Keyword(s):  
Rhesus Monkey ◽  
Fusion Protein ◽  
Blood Brain Barrier ◽  
Neurotrophic Factor ◽  
Brain Barrier ◽  
Blood Brain ◽  
Glial Derived Neurotrophic Factor

scholarly journals Monoclonal Antibody-Glial-Derived Neurotrophic Factor Fusion Protein Penetrates the Blood-Brain Barrier in the Mouse

2010 ◽  
Vol 38 (4) ◽  
pp. 566-572 ◽  
Author(s):  
Qing-Hui Zhou ◽  
Ruben J. Boado ◽  
Jeff Zhiqiang Lu ◽  
Eric Ka-Wai Hui ◽  
William M. Pardridge
Keyword(s):  
Monoclonal Antibody ◽  
Fusion Protein ◽  
Blood Brain Barrier ◽  
Neurotrophic Factor ◽  
Brain Barrier ◽  
Blood Brain ◽  
Glial Derived Neurotrophic Factor

scholarly journals Dual Roles of Astrocyte-Derived Factors in Regulation of Blood-Brain Barrier Function after Brain Damage

2019 ◽  
Vol 20 (3) ◽  
pp. 571 ◽  
Author(s):  
Shotaro Michinaga ◽  
Yutaka Koyama
Keyword(s):  
Brain Damage ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Blood Brain ◽  
Secondary Damage ◽  
The Central Nervous System ◽  
Bbb Permeability ◽  
Novel Therapeutic Strategies ◽  
Glial Derived Neurotrophic Factor ◽  
Endothelial Growth Factors

The blood-brain barrier (BBB) is a major functional barrier in the central nervous system (CNS), and inhibits the extravasation of intravascular contents and transports various essential nutrients between the blood and the brain. After brain damage by traumatic brain injury, cerebral ischemia and several other CNS disorders, the functions of the BBB are disrupted, resulting in severe secondary damage including brain edema and inflammatory injury. Therefore, BBB protection and recovery are considered novel therapeutic strategies for reducing brain damage. Emerging evidence suggests key roles of astrocyte-derived factors in BBB disruption and recovery after brain damage. The astrocyte-derived vascular permeability factors include vascular endothelial growth factors, matrix metalloproteinases, nitric oxide, glutamate and endothelin-1, which enhance BBB permeability leading to BBB disruption. By contrast, the astrocyte-derived protective factors include angiopoietin-1, sonic hedgehog, glial-derived neurotrophic factor, retinoic acid and insulin-like growth factor-1 and apolipoprotein E which attenuate BBB permeability resulting in recovery of BBB function. In this review, the roles of these astrocyte-derived factors in BBB function are summarized, and their significance as therapeutic targets for BBB protection and recovery after brain damage are discussed.

Transport of brain-derived neurotrophic factor across the blood–brain barrier

1998 ◽  
Vol 37 (12) ◽  
pp. 1553-1561 ◽  
Author(s):  
Weihong Pan ◽  
William A Banks ◽  
Melita B Fasold ◽  
Jonathan Bluth ◽  
Abba J Kastin
Keyword(s):  
Blood Brain Barrier ◽  
Neurotrophic Factor ◽  
Brain Derived Neurotrophic Factor ◽  
Brain Barrier ◽  
Blood Brain

Inhibition of Notch and tumor regression

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e14623-e14623
Author(s):  
A. A. Epenetos ◽  
C. Kousparou ◽  
S. Stylianou
Keyword(s):  
Stem Cells ◽  
Fusion Protein ◽  
Notch Signaling ◽  
Blood Brain Barrier ◽  
Tumor Regression ◽  
The Self ◽  
Brain Barrier ◽  
Self Renewal ◽  
Blood Brain ◽  
Repeat Administration

e14623 Background: Notch signaling is an evolutionary-conserved pathway in vertebrates and invertebrates which is involved many developmental processes, including cell fate decisions, apoptosis, proliferation, and stem-cell self renewal. There is increasing evidence that the same molecular pathways regulating the self renewal of stem cells are also being employed in cancer progression. The Notch signal transduction pathway has been implicated in the self-renewal of stem cells in hematopoietic, skin, neural, germ and breast tissue. Increasing evidence suggests that the Notch signaling pathway is frequently up regulated in many forms of cancer including acute T-cell lymphoblastic leukemia, cervical, prostate, lung, breast and others. Thus,inhibition of the pathway could provide a novel treatment of cancer and cancer stem cells. Methods: We have genetically engineered a fusion protein, consisting of the Drosophila transcription factor Antennapedia (ANTP) and with the truncated version of Mastermind-like (MAML) that behaves in a dominant negative (DN) fashion and inhibits Notch activation (ANTP/DN MAML, TR4). This novel fusion protein has been tested for its ability to target tumor cells in vitro and in vivo. Results: Our data show that ANTP/DN MAML fusion protein, TR4 contains signals for proper cell targeting, internalization and nuclear transport. Furthermore, TR4 inhibits human mammary and colon xenograft tumor growth and metastases in immuno deficient mice.TR4 presence and activity was also detected in the brains of treated animals demonstrating that TR4 can cross the blood-brain barrier and potentially eliminate brain tumors and metastases, unlike other anticancer drugs and biological such as monoclonal antibodies that cannot cross the blood brain barrier. TR4 was found to be non- immunogenic following repeat administration in healthy animals. At very high doses (>10x therapeutic dose) it caused anorexia and weight loss in mice. Conclusions: The TR4 protein, a Notch inhibitor, can induce tumor regression and resolution of breast and colon cancer xenografts. It is non- immunogenic following repeat administration and has acceptable toxicity profile. No significant financial relationships to disclose.

Blood-Brain Barrier Molecular Trojan Horse Enables Imaging of Brain Uptake of Radioiodinated Recombinant Protein in the Rhesus Monkey

2013 ◽  
Vol 24 (10) ◽  
pp. 1741-1749 ◽  
Author(s):  
Ruben J. Boado ◽  
Eric K.-W. Hui ◽  
Jeff Zhiqiang Lu ◽  
Rachita K. Sumbria ◽  
William M. Pardridge
Keyword(s):  
Recombinant Protein ◽  
Rhesus Monkey ◽  
Blood Brain Barrier ◽  
Trojan Horse ◽  
Brain Barrier ◽  
Brain Uptake ◽  
Blood Brain

GDNF fusion protein for targeted-drug delivery across the human blood–brain barrier

2008 ◽  
Vol 100 (2) ◽  
pp. 387-396 ◽  
Author(s):  
Ruben J. Boado ◽  
Yun Zhang ◽  
Yufeng Zhang ◽  
Yuntao Wang ◽  
William M. Pardridge
Keyword(s):  
Drug Delivery ◽  
Fusion Protein ◽  
Blood Brain Barrier ◽  
Human Blood ◽  
Targeted Drug Delivery ◽  
Brain Barrier ◽  
Blood Brain ◽  
Targeted Drug
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