Review
Chemistry, Multidisciplinary
Nazneen Pathan, Pravin Shende
Summary: P-Glycoprotein plays a vital role in the blood-brain barrier, protecting the central nervous system from infections and external toxic molecules. It is essential in various brain-related conditions but also poses a significant challenge in drug delivery across the blood-brain barrier.
JOURNAL OF CONTROLLED RELEASE
(2021)
Article
Biochemistry & Molecular Biology
Vinicius Cavicchioli Azevedo, Christopher J. Kennedy
Summary: This study investigated the neuroprotective effects of inducing the blood-brain barrier protein P-gp with CTZ in zebrafish against the neurotoxicant IVM. The results showed that P-gp induction may have limited protective effects on the zebrafish CNS from IVM. Additionally, the effects of IVM and P-gp induction were not influenced by feeding or fasting.
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Yuheng Shan, Yuying Cen, Yanjin Zhang, Ruishu Tan, Jiahua Zhao, Zhiyong Nie, Jiatang Zhang, Shengyuan Yu
Summary: The study demonstrated that P-glycoprotein inhibition can enhance the brain concentration of ceftriaxone (CFX) and increase its penetration across the blood-brain barrier (BBB). Cyclosporin A increased both the brain concentration and the ratio of unbound brain to unbound blood concentration of CFX in a dose-dependent manner, while verapamil only increased the brain concentration of CFX without affecting the penetration ratio across the BBB. Future studies with more selective P-gp inhibitors or knockout mouse models are needed to further investigate the impact of P-gp inhibition on CFX penetration across the BBB.
NEUROCHEMICAL RESEARCH
(2022)
Article
Geriatrics & Gerontology
Liangliang Huang, Yan Chen, Rui Liu, Binbin Li, Xuan Fei, Xiang Li, Ge Liu, Yunman Li, Baohui Xu, Weirong Fang
Summary: Increased expression of P-gp after ischemic injury leads to dysfunction and hyperpermeability of the BBB by suppressing Akt/mTOR-induced endothelial autophagy.
Article
Biochemistry & Molecular Biology
Vinicius C. Azevedo, Christopher J. Kennedy
Summary: This study examines the role of the blood-brain barrier ATP-binding cassette protein transporter P-glycoprotein (P-gp) in protecting zebrafish from the neurotoxic effects of the pesticide ivermectin. The results show that the presence of the competitive inhibitor cyclosporin A (CsA) increases the adverse effects of ivermectin on swimming and behavior in the fish. Additionally, fasting does not affect the protective role of P-gp against ivermectin. These findings suggest that P-gp plays a crucial role in defending fish from environmental neurotoxicants.
FISH PHYSIOLOGY AND BIOCHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Jae Pyun, Huijing Koay, Pranav Runwal, Celeste Mawal, Ashley I. Bush, Yijun Pan, Paul S. Donnelly, Jennifer L. Short, Joseph A. Nicolazzo
Summary: Cu(ATSM) enhances the expression and function of P-gp at the blood-brain barrier, which has important implications for CNS drug delivery and clearance of A beta in AD.
Article
Toxicology
Laurens F. M. Verscheijden, Jan B. Koenderink, Saskia N. de Wildt, Frans G. M. Russel
Summary: The study found that BBB Pgp activity is species-specific, and an age-dependent PBPK model can optimize predictions of brain drug concentrations. The methods used in the study have the potential to address challenges in extrapolating brain drug disposition and toxicity.
ARCHIVES OF TOXICOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Amanda B. Chai, Richard Callaghan, Ingrid C. Gelissen
Summary: This review summarizes the current understanding of P-gp regulation in the brain, including transcriptional, post-transcriptional, and post-translational mechanisms, aiming to provide new strategies for optimizing therapeutic outcomes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Ryuta Jomura, Shin-ichi Akanuma, Bjorn Bauer, Yukiko Yoshida, Yoshiyuki Kubo, Ken-ichi Hosoya
Summary: The study investigated the transport of phenytoin across the blood-brain barrier (BBB), identifying that MCT8 participates in the efflux of phenytoin from the brain to the blood. Meanwhile, P-gp did not affect the efflux of phenytoin from the brain.
PHARMACEUTICAL RESEARCH
(2021)
Article
Chemistry, Multidisciplinary
Severin Mairinger, Irene Hern, Thomas Filip, Michael Sauberer, Mathilde Lobsch, Johann Stanek, Thomas Wanek, Johannes A. Sake, Thomas Pekar, Carsten Ehrhardt, Oliver Langer
Summary: This study used positron emission tomography (PET) imaging to investigate the influence of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) on the pulmonary distribution of inhaled drugs. The results showed functional activity of P-gp and BCRP in the lungs and suggested that these transporters play a role in limiting the uptake of drugs in the lungs, similar to the blood-brain barrier. The study highlights the importance of pulmonary efflux transporters in the efficacy and safety of inhaled drugs.
JOURNAL OF CONTROLLED RELEASE
(2022)
Article
Cell Biology
Chunfu Li, Yongzhi Wang, Huiting Liu, Xinghua Zhang, Dalai Baolige, Shihua Zhao, Wei Hu, Yang Yang
Summary: Lab-attenuated rabies virus (RABV) is a less pathogenic variant compared to wild-type RABV, and through serial passage in mice brains, a safe and well-replicating strain was developed with specific amino acid substitutions on the G protein. This decreased pathogenicity was linked to increased RABV-G expression, higher apoptosis levels in infected cells, and effects on DCs and blood-brain barrier permeability.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Chemistry, Medicinal
Saba Hammad, Aloise Mabondzo, Rifat Hamoudi, Rania Harati
Summary: It has been found that miR-27a-3p regulates the expression and activity of P-gp at the blood-brain barrier by mediating Glycogen Synthase Kinase 3 Beta (GSK3β) inhibition and activating Wnt/β-catenin signaling.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
Review
Multidisciplinary Sciences
Iman Imtiyaz Ahmed Juvale, Azzmer Azzar Abdul Hamid, Khairul Bariyyah Abd Halim, Ahmad Tarmizi Che Has
Summary: The multidrug resistance phenomenon poses a significant threat to the pharmaceutical industry and is mediated by multidrug transporters like P-glycoprotein. P-glycoprotein, with its versatile binding sites, accommodates various compounds and plays crucial roles in both multidrug resistant diseases and physiological functions in the human body.
Article
Pharmacology & Pharmacy
Casey-Tyler Berezin, Nikolas Bergum, Glenda M. Torres Lopez, Jozsef Vigh
Summary: Opioids are effective analgesics, but their dangerous side effects need to be considered. Research on opioid pharmacokinetics provides crucial information on drug effects. This study found that morphine accumulates in the mouse retina at higher concentrations than in the brain and that reduced P-gp expression may be the cause. P-gp was identified as the main opioid transporter at the blood-retina barrier, and its expression correlated with morphine concentration in the retina.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Stephanie A. Newman, Yijun Pan, Jennifer L. Short, Joseph A. Nicolazzo
Summary: These studies demonstrate that iron negatively regulates P-gp expression at the BBB, potentially impacting CNS drug delivery and brain beta-amyloid clearance.
PHARMACEUTICAL RESEARCH
(2021)