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, 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
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)
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
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
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)
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
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
Multidisciplinary Sciences
Qiuying Zhao, Weiye Dai, Hui Yu Chen, Russell E. Jacobs, Berislav V. Zlokovic, Brett T. Lund, Axel Montagne, Alexandre Bonnin
Summary: Gestational maternal immune activation in mice leads to persistent brain inflammation and neuropathological changes in adult offspring. This study reveals that the disruption of blood-brain barrier (BBB) function is involved in this process, which is caused by increased microglial activation and abnormal prenatal BBB formation driven by COX2 expression.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(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)
Review
Biochemistry & Molecular Biology
Benjamin Fredrick Gruenbaum, Alexander Zlotnik, Amit Frenkel, Ilya Fleidervish, Matthew Boyko
Summary: Depression is a leading cause of disability globally, yet conventional antidepressant therapies often prove ineffective. Recent studies have identified promising glutamate-based approaches as alternatives to traditional treatments. This review explores the involvement of the glutamate system in depression and offers new insights into therapeutic strategies, particularly in relation to blood-brain barrier permeability. The authors propose further investigation into the use of blood glutamate scavengers for conditions associated with impaired blood-brain barrier function, including depression following stroke or traumatic brain injury, and neurodegenerative diseases.
Article
Pharmacology & Pharmacy
Jin-Zi Ji, Yi-Fei Li, Li-Ping Jiang, Ting Tai, Peng-Xin Ge, Qiong-Yu Mi, Ting Zhu, Hong-Guang Xie
Summary: In this study, P-gp-deficient mice showed increased systemic exposure of clopidogrel active metabolite H4 and enhanced antiplatelet effect of clopidogrel, possibly through up-regulation of Cyp3a11 and down-regulation of Ces1, despite no significant differences in intracellular clopidogrel concentrations between KO and WT mice. These findings suggest a potential inverse correlation between P-gp activity and the formation of H4 and antiplatelet efficacy of clopidogrel in clinical settings due to P-gp and CYP3A4 interaction.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Veterinary Sciences
Sofie F. M. Bhatti, Luisa De Risio, Karen Munana, Jacques Penderis, Veronika M. Stein, Andrea Tipold, Mette Berendt, Robyn G. Farquhar, Andrea Fischer, Sam Long, Wolfgang Loescher, Paul J. J. Mandigers, Kaspar Matiasek, Akos Pakozdy, Edward E. Patterson, Simon Platt, Michael Podell, Heidrun Potschka, Clare Rusbridge, Holger A. Volk
BMC VETERINARY RESEARCH
(2015)
Article
Veterinary Sciences
Mette Berendt, Robyn G. Farquhar, Paul J. J. Mandigers, Akos Pakozdy, Sofie F. M. Bhatti, Luisa De Risio, Andrea Fischer, Sam Long, Kaspar Matiasek, Karen Munana, Edward E. Patterson, Jacques Penderis, Simon Platt, Michael Podell, Heidrun Potschka, Marti Batlle Pumarola, Clare Rusbridge, Veronika M. Stein, Andrea Tipold, Holger A. Volk
BMC VETERINARY RESEARCH
(2015)
Article
Veterinary Sciences
Luisa De Risio, Sofie Bhatti, Karen Munana, Jacques Penderis, Veronika Stein, Andrea Tipold, Mette Berendt, Robyn Farqhuar, Andrea Fischer, Sam Long, Paul J. J. Mandigers, Kaspar Matiasek, Rowena M. A. Packer, Akos Pakozdy, Ned Patterson, Simon Platt, Michael Podell, Heidrun Potschka, Marti Pumarola Batlle, Clare Rusbridge, Holger A. Volk
BMC VETERINARY RESEARCH
(2015)
Article
Medicine, Research & Experimental
Josephine D. Salvamoser, Janine Avemary, Hiram Luna-Munguia, Bettina Pascher, Thekla Getzinger, Tom Pieper, Manfred Kudematsch, Gerhard Kuger, Heidrun Potschka
MOLECULAR PHARMACEUTICS
(2015)
Article
Neurosciences
E. L. von Rueden, R. M. Bogdanovic, C. T. Wotjak, H. Potschka
NEUROBIOLOGY OF DISEASE
(2015)
Article
Neurosciences
E. L. von Rueden, M. Jafari, R. M. Bogdanovic, C. T. Wotjak, H. Potschka
NEUROBIOLOGY OF DISEASE
(2015)
Article
Neurosciences
Maruja L. Rettenbeck, Eva-Lotta von Rueden, Silvia Bienas, Regina Carlson, Veronika M. Stein, Andrea Tipold, Heidrun Potschka
NEUROSCIENCE LETTERS
(2015)
Article
Neurosciences
Katharina Boes, Vera Russmann, Tanja Ongerth, Thomas Licko, Josephine D. Salvamoser, Claudia Siegl, Heidrun Potschka
NEUROSCIENCE LETTERS
(2015)
Article
Immunology
Andreas Walker, Vera Russmann, Cornelia A. Deeg, Christine von Toerne, Kristina J. H. Kleinwort, Christoph Szober, Maruja L. Rettenbeck, Eva-Lotta von Rueden, Joanna Goc, Tanja Ongerth, Katharina Boes, Josephine D. Salvamoser, Annamaria Vezzani, Stefanie M. Hauck, Heidrun Potschka
BRAIN BEHAVIOR AND IMMUNITY
(2016)
Article
Clinical Neurology
Vera Russmann, Josephine D. Salvamoser, Maruja L. Rettenbeck, Takafumi Komori, Heidrun Potschka
Article
Pharmacology & Pharmacy
Vera Russmann, Joanna Goc, Katharina Boes, Tanja Ongerth, Josephine D. Salvamoser, Claudia Siegl, Heidrun Potschka
EUROPEAN JOURNAL OF PHARMACOLOGY
(2016)
Article
Toxicology
Kathrin Backes, Helga Lorenz, Loic Laplanche, Thomas J. Hudzik, Heidrun Potschka, Katja Hempel
TOXICOLOGY LETTERS
(2016)
Article
Agriculture, Dairy & Animal Science
Lukas Breuer, Lucas Moesch, Janosch Kunczik, Verena Buchecker, Heidrun Potschka, Michael Czaplik, Carina Barbosa Pereira
Summary: By analyzing visible breathing movement in the thorax, researchers used camera-based methods to monitor the respiratory rate of laboratory rats. This study contributes to the development of non-invasive monitoring methods for rodents, reducing the need for implanted sensors and minimizing stress and pain for the animals.
Article
Agriculture, Dairy & Animal Science
Larissa Weiss, Anna M. Saller, Julia Werner, Stephanie C. Suess, Judith Reiser, Sandra Kollmansperger, Malte Anders, Heidrun Potschka, Thomas Fenzl, Benjamin Schusser, Christine Baumgartner
Summary: This research aimed to determine when chickens acquire the ability to sense pain during embryonic development. By applying mechanical stimuli to chicken embryos and measuring changes in blood pressure and heart rate, it was found that embryos at around two days before hatching showed significant responses to noxious stimuli, indicating the emergence of nociception.
Article
Pharmacology & Pharmacy
Hiram Luna-Munguia, Josephine D. Salvamoser, Bettina Pascher, Tom Pieper, Thekla Getzinger, Manfred Kudernatsch, Gerhard Kluger, Heidrun Potschka
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2015)