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
Chemistry, Multidisciplinary
Behnam Noorani, Ekram Ahmed Chowdhury, Faleh Alqahtani, Md Sanaullah Sajib, Yeseul Ahn, Ehsan Nozohouri, Dhavalkumar Patel, Constantinos Mikelis, Reza Mehvar, Ulrich Bickel
Summary: This study evaluated a three-compartmental semi-physiological model for analyzing the uptake clearance and efflux from brain tissue of hydrophilic markers, sucrose and mannitol, in comparison to non-compartmental techniques. The model accurately described the experimental data, providing estimates for uptake clearance and brain efflux of the two markers. The results showed significant differences in uptake clearance between sucrose and mannitol, while brain efflux clearance values were not statistically different.
PHARMACEUTICAL RESEARCH
(2022)
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
Medicine, Research & Experimental
Wei Chu, Xuemei Sun, Xiaoxiao Zhu, Yu Chen Zhao, Jingcheng Zhang, Qin Kong, Lanlan Zhou
Summary: The study showed that the glycoprotein (GP) Ib antagonist anfibatide (ANF) mitigated blood-brain barrier (BBB) disruption after cerebral ischemia/reperfusion (CI/R) injury through activation of the Epac signaling pathway. ANF treatment improved tight junction protein expression, suppressed actin rearrangement, reduced brain tissue permeability, and alleviated brain edema. Additionally, ANF upregulated Epac1 protein expression in the ischemic cerebral cortex, demonstrating its protective effects on BBB integrity.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
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
Biochemistry & Molecular Biology
Itzik Cooper, Katayun Cohen-Kashi Malina, Yishai Levin, Alexandra Gabashvili, Boaz Mohar, Alfredo Cagnotto, Mario Salmona, Vivian Teichberg
Summary: This study investigated the mechanisms of interaction between PrP 106-126 and the blood-brain barrier (BBB). It was found that PrP 106-126 treatment reduced BBB function, decreased cAMP levels, increased nitric oxide (NO) levels, and altered the activation modes of the GTPases Rac1 and RhoA. Proteomic analysis revealed significant changes in cytoskeleton-related protein expression. These findings highlight the nature of the interaction between PrP 106-126 and the BBB, and underscore the importance of the cytoskeleton in endothelial response to prion-induced stress.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(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)
