OBJECTIVE: This study was undertaken to assess the role of p97 (also known as melanotransferrin) in the transfer of iron into the brain, because the passage of most large molecules is limited by the presence of the blood-brain barrier, including that of the serum iron transporter transferrin. METHODS: To study the function of the soluble form of p97, we followed the uptake of radioiodinated and 55Fe loaded p97 and transferrin by the brain during a 24-hour period. RESULTS: We show that the soluble form of p97 has the ability to transcytose across the murine blood-brain barrier, and its transcytosis can be inhibited in a specific manner. We also provide evidence that p97 transports iron into the brain more efficiently than transferrin. CONCLUSIONS: These data support the idea that p97 is an important iron transporter across the blood-brain barrier in normal physiology and possibly in neurodegenerative diseases, such as Alzheimer disease, in which iron homeostasis in the brain becomes disrupted.
OBJECTIVE: This study was undertaken to assess the role of p97 (also known as melanotransferrin) in the transfer of iron into the brain, because the passage of most large molecules is limited by the presence of the blood-brain barrier, including that of the serum iron transporter transferrin. METHODS: To study the function of the soluble form of p97, we followed the uptake of radioiodinated and 55Fe loaded p97 and transferrin by the brain during a 24-hour period. RESULTS: We show that the soluble form of p97 has the ability to transcytose across the murine blood-brain barrier, and its transcytosis can be inhibited in a specific manner. We also provide evidence that p97 transports iron into the brain more efficiently than transferrin. CONCLUSIONS: These data support the idea that p97 is an important iron transporter across the blood-brain barrier in normal physiology and possibly in neurodegenerative diseases, such as Alzheimer disease, in which iron homeostasis in the brain becomes disrupted.
Authors: George Thom; Mei-Mei Tian; Jon P Hatcher; Natalia Rodrigo; Matthew Burrell; Ian Gurrell; Timothy Z Vitalis; Thomas Abraham; Wilfred A Jefferies; Carl I Webster; Reinhard Gabathuler Journal: J Cereb Blood Flow Metab Date: 2018-05-30 Impact factor: 6.200
Authors: Julie A Gaasch; Paul R Lockman; Werner J Geldenhuys; David D Allen; Cornelis J Van der Schyf Journal: Neurochem Res Date: 2007-04-03 Impact factor: 3.996
Authors: Mohamed Ismail Nounou; Chris E Adkins; Evelina Rubinchik; Tori B Terrell-Hall; Mohamed Afroz; Tim Vitalis; Reinhard Gabathuler; Mei Mei Tian; Paul R Lockman Journal: Pharm Res Date: 2016-08-15 Impact factor: 4.200
Authors: 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 Journal: Front Neurosci Date: 2021-06-02 Impact factor: 4.677