Article
Neurosciences
Fangfang Zhao, Liyuan Zhong, Yumin Luo
Summary: The blood-brain barrier is a complex neurovascular unit that protects neurons and maintains stability of the central nervous system, with endothelial glycocalyx playing a critical role in its structure and functions. Damage to glycocalyx can lead to dysfunction and neurological diseases, highlighting the importance of research in providing theoretical basis for diagnosis and treatment.
CNS NEUROSCIENCE & THERAPEUTICS
(2021)
Article
Neurosciences
Chelsea M. Phillips, Allison M. Johnson, Svetlana M. Stamatovic, Richard F. Keep, Anuska V. Andjelkovic
Summary: This study reveals that the absence of CCM3 leads to structural defects in the brain endothelial barrier, increasing the risk of vascular leakage. The upregulation of GJA1-20 k is found to disrupt the balance between gap junctions and tight junctions, destabilizing the tight junction complex and increasing brain endothelial barrier permeability.
NEUROBIOLOGY OF DISEASE
(2023)
Article
Cardiac & Cardiovascular Systems
Maarja A. Mae, Liqun He, Sofia Nordling, Elisa Vazquez-Liebanas, Khayrun Nahar, Bongnam Jung, Xidan Li, Bryan C. Tan, Juat Chin Foo, Amaury Cazenave-Gassiot, Markus R. Wenk, Yvette Zarb, Barbara Lavina, Susan E. Quaggin, Marie Jeansson, Chengua Gu, David L. Silver, Michael Vanlandewijck, Eugene C. Butcher, Annika Keller, Christer Betsholtz
Summary: Through single-cell RNA sequencing and other methods, the study revealed the transcriptional, morphological, and functional changes in brain endothelial cells in response to pericyte deficiency. Endothelial cells without pericyte contact maintain a BBB-specific gene expression profile and acquire a venous-shifted molecular pattern.
CIRCULATION RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Roberta Lugano, Kalyani Vemuri, Stefano Barbera, Maurizio Orlandini, Elisabetta Dejana, Lena Claesson-Welsh, Anna Dimberg
Summary: CD93 regulates the stability of VE-cadherin at endothelial junctions by interacting with VE-cadherin and limiting its phosphorylation and turnover. CD93 deficiency leads to increased phosphorylation of VE-cadherin, displacing it from endothelial cell-cell contacts and disrupting endothelial junctions, resulting in enhanced blood-brain barrier permeability. This mechanism is regulated through the Rho/Rho kinase-dependent pathway.
Article
Neurosciences
Zhongyan Zhao, Chanji Wu, Xiangying He, Eryi Zhao, Shijun Hu, Yeguang Han, Ting Wang, Yanquan Chen, Tao Liu, Shixiong Huang
Summary: Through investigating the role of microRNA let-7f in endothelial cell dysfunction induced by oxygen-glucose deprivation and reoxygenation (OGD/R), this study found that let-7f alleviates vascular endothelial dysfunction by downregulating HMGA2 expression, leading to improved cell viability, reduced apoptosis, and maintained endothelial permeability. Additionally, let-7f's effects on endothelial dysfunction were reversed by HMGA2 overexpression, demonstrating the regulatory relationship between let-7f and HMGA2 in OGD/R-induced injuries.
Review
Cell Biology
Ece Bayir, Aylin Sendemir
Summary: The blood-brain barrier is a highly selective cellular monolayer unique to the central nervous system microvasculature, mediating communication with the body by regulating the passage of molecules. Recent studies have highlighted the importance of intermediate filaments in the formation and function of cell-cell junctions, particularly vimentin in endothelial cells. Intermediate filaments may have been overlooked as key targets in regulating blood-brain barrier permeability in health and disease.
Article
Biochemistry & Molecular Biology
Pablo Torres-Vergara, Felipe Troncoso, Jesenia Acurio, Ellen Kupka, Lina Bergman, Anna-Karin Wikstro, Carlos Escudero
Summary: Disruption of blood-brain barrier is a central issue in the pathophysiology of acute cerebral complications in women with preeclampsia. The underlying mechanisms are unclear. This study found that plasma from women with preeclampsia increased cell apoptosis and permeability in human brain endothelial cells, possibly through activation of VEGFR2. The different phosphorylation patterns of VEGFR2 suggest that further investigation is needed to determine its specific activation status.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2022)
Article
Immunology
Nuria Villalba, Yonggang Ma, Sarah A. Gahan, Aurelie Joly-Amado, Sam Spence, Xiaoyuan Yang, Kevin R. Nash, Sarah Y. Yuan
Summary: This study investigated the effects of lung infection on blood-brain barrier disruption and behavioral changes, and found that systemic bacterial infection may contribute to lung-brain axis inflammatory response through cytokine release.
JOURNAL OF NEUROINFLAMMATION
(2023)
Review
Biochemistry & Molecular Biology
Ruicheng Yang, Jundan Wang, Fen Wang, Huipeng Zhang, Chen Tan, Huanchun Chen, Xiangru Wang
Summary: Despite advances in treatment, bacterial meningitis remains a serious infection that poses a risk to life. The blood-brain barrier plays an important role in the pathogenesis of bacterial meningitis through increased permeability. Recent studies have shown that targeting the factors contributing to enhanced blood-brain barrier permeability is an effective complement to antimicrobial therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Steffi Schumacher, Hanane Tahiri, Pascal Ezan, Nathalie Rouach, Katja Witschas, Luc Leybaert
Summary: Therapeutic brain irradiation induces reorganization of astrocytic vesicular transport, leading to VEGF-A release and barrier leakage, and this process can be inhibited by targeting astrocyte connexin 43 (Cx43).
Article
Immunology
Rui-Cheng Yang, Kun Huang, Hui-Peng Zhang, Liang Li, Yu-Fei Zhang, Chen Tan, Huan-Chun Chen, Mei-Lin Jin, Xiang-Ru Wang
Summary: The study found that SARS-CoV-2 infection can cause dysfunction of the blood-brain barrier, increasing its permeability, which provides new insights into the neuropathogenesis of SARS-CoV-2.
JOURNAL OF NEUROINFLAMMATION
(2022)
Article
Neurosciences
Lena Hansen, Niklas Lohfink, Rajkumar Vutukuri, Roxane-Isabelle Kestner, Sandra Trautmann, Max Hecht, Pia Viktoria Wagner, Daniel Spitzer, Maryam Ibrahim Khel, Jadranka Macas, Nerea Ferreiros, Robert Gurke, Stefan Guenther, Waltraud Pfeilschifter, Kavi Devraj
Summary: This study provides novel data on the expression, localization, and function of S1P receptor 4 (S1P4) in brain microvascular endothelial cells (BMECs). The results show that S1P4 plays an important role in maintaining blood-brain barrier (BBB) permeability, and its downregulation is associated with BBB dysfunction. These findings reveal the therapeutic potential of S1P4 as a novel target for CNS diseases associated with BBB dysfunction.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Multidisciplinary Sciences
Seu-Na Lee, Hwa-Jin Cho, Hyeongseop Jeong, Bumhan Ryu, Hyuk-Joon Lee, Minsoo Kim, Jejoong Yoo, Jae-Sung Woo, Hyung Ho Lee
Summary: Cx36, responsible for signal transmission in electrical synapses, forms interneuronal gap junctions. Cryo-EM structures of Cx36 reveal a closed state with obstructed channel pores and excluded N-terminal helices, and an open state with acidic pore and weakened protomer-protomer interaction. Lipids may play a potential role in Cx36 channel gating.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Yunfei Li, Yifan Xia, Huixiang Zhu, Eric Luu, Guangyao Huang, Yan Sun, Kevin Sun, Sander Markx, Kam W. Leong, Bin Xu, Bingmei M. Fu
Summary: The integrity of the blood-brain barrier is compromised in patients with 22q11.2 deletion syndrome associated with schizophrenia, leading to increased solute permeability, decreased trans-endothelial electrical resistance, and disruption of tight junction proteins and endothelial glycocalyx.
Article
Biochemistry & Molecular Biology
Panpan Lin, Rongbang Tan, Ping Yu, Yanyu Li, Yuqian Mo, Wen Li, Jingjing Zhang
Summary: The blood-brain barrier is essential for protecting the central nervous system, but it also hinders efficient drug delivery. This study demonstrates that a mutated fragment of Clostridium perfringens enterotoxin can regulate the dynamics of the endothelial tight junction protein claudin-5 and influence blood-brain barrier permeability.
Review
Cell Biology
Peter Vandenabeele, Geert Bultynck, Savvas N. Savvides
Summary: Regulated cell death (RCD) relies on the activation and recruitment of pore-forming proteins (PFPs) to execute specific cell death pathways. This review discusses the structural rearrangements incurred by RCD-related PFPs and describes the mechanisms behind the conversion from an autoinhibited state to a membrane-embedded state. It also highlights the formation and maturation of membrane pores and the implications of different cell death modalities on physiological and pathophysiological processes.
NATURE REVIEWS MOLECULAR CELL BIOLOGY
(2023)
Editorial Material
Biochemistry & Molecular Biology
Geert Bultynck, Shazia Khan, M. Lienhard Schmitz
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2023)
Article
Cell Biology
Ian de Ridder, Martijn Kerkhofs, Fernanda O. Lemos, Jens Loncke, Geert Bultynck, Jan B. Parys
Summary: Endoplasmic reticulum (ER)-mitochondria contact sites are crucial for Ca2+ flux and involve multiple proteins. Inositol 1,4,5-trisphosphate receptors (IP3Rs) play a central role in tethering ER and mitochondria and transporting Ca2+. The IP3R-GRP75-VDAC1 complex acts as a hub for stabilizing and regulating Ca2+ transfer into mitochondria.
Article
Neurosciences
D. Chernyuk, M. Callens, M. Polozova, A. Gordeev, M. Chigriai, A. Rakovskaya, A. Ilina, E. Pchitskaya, C. Van den Haute, T. Vervliet, G. Bultynck, I. Bezprozvanny
Summary: Alzheimer's disease is the most common cause of dementia, and dysregulation of intracellular Ca2+ signaling is an early feature in the pathology. This study examined the hypothesis that expression of Bcl-2 proteins can normalize dysregulated Ca2+ signaling in a mouse model of AD and potentially prevent or slow the progression of the disease. The results indicate that Bcl-2 protein expression leads to synaptoprotective and amyloid-protective effects in the mouse model.
IBRO NEUROSCIENCE REPORTS
(2023)
Editorial Material
Cell Biology
Jan B. Parys, Geert Bultynck
Article
Cell Biology
Julius Ronkko, Yago Rodriguez, Tiina Rasila, Ruben Torregrosa-Munumer, Jana Pennonen, Jouni Kvist, Emilia Kuuluvainen, Ludo Van Den Bosch, Ville Hietakangas, Geert Bultynck, Henna Tyynismaa, Emil Ylikallio
Summary: Through the development of single and triple Inositol 1,4,5-trisphosphate receptors (IP3Rs) knockouts in human induced pluripotent stem cells (hiPSC), it was found that IP3Rs are not essential for hiPSC identity and pluripotency, but regulate mitochondrial metabolism. This set of knockout hiPSC is a valuable resource for investigating IP3Rs in human cell types of interest.
Article
Neurosciences
Steffi Schumacher, Hanane Tahiri, Pascal Ezan, Nathalie Rouach, Katja Witschas, Luc Leybaert
Summary: Therapeutic brain irradiation induces reorganization of astrocytic vesicular transport, leading to VEGF-A release and barrier leakage, and this process can be inhibited by targeting astrocyte connexin 43 (Cx43).
Article
Biochemistry & Molecular Biology
Alessio Lissoni, Siyu Tao, Rosalie Allewaert, Katja Witschas, Luc Leybaert
Summary: Cx43 hemichannels (HCs) and Panx1 channels, two genetically distant protein families, have been debated for their similarities in expression, membrane topology, and electrical properties. This study used mimetic peptides Gap19 and (10)Panx1 to investigate their cross-effects on Cx43 HCs and Panx1 channels. The results showed that Gap19 significantly inhibited Panx1 channels, while high concentrations of (10)Panx1 significantly reduced the activity of Cx43 HCs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Flore Sneyers, Martijn Kerkhofs, Femke Speelman-Rooms, Kirsten Welkenhuyzen, Rita La Rovere, Ahmed Shemy, Arnout Voet, Guy Eelen, Mieke Dewerchin, Stephen W. G. Tait, Bart Ghesquiere, Martin D. Bootman, Geert Bultynck
Summary: Intracellular Ca2+ signals play a crucial role in various cellular processes. Research has shown that BAPTAi can induce apoptosis in cancer cells by inhibiting mTORC1 activity and impairing glycolysis, independent of Ca2+ signaling. Additionally, direct inhibition of PFKFB3 emerges as a potential therapeutic target in MCL-1-dependent cancers.
CELL DEATH & DISEASE
(2023)
Article
Cell Biology
Elzbieta Kania, Jaclyn S. Long, David G. McEwan, Kirsten Welkenhuyzen, Rita La Rovere, Tomas Luyten, John Halpin, Evy Lobbestael, Veerle Baekelandt, Geert Bultynck, Kevin M. Ryan, Jan B. Parys
Summary: Mutations in the LRRK2 gene are the most common genetic cause of Parkinson's disease, and they also have importance in Crohn's disease and cancer. A study found that the phosphorylation status of LRRK2 affects its function, and the S910/S935/S955/S973 phosphorylation sites play a crucial role in regulating LRRK2-mediated autophagy. Cells with quadruple LRRK2 phosphomutations showed impaired autophagy during starvation, while treatment with LRRK2 kinase inhibitors did not affect autophagy. Increased LRRK2 kinase activity was found to drive autophagy impairment through phosphorylation of downstream targets Rab8a and Rab10.
CELL DEATH & DISEASE
(2023)
Article
Cell Biology
Fernanda O. Lemos, Ian de Ridder, Martin D. Bootman, Geert Bultynck, Jan B. Parys
Summary: PKM2 regulates calcium handling in the cytosol and mitochondria separately, while TAT-D5SD induces apoptosis by disrupting the PKM2:IP3R interaction.
Article
Medicine, Research & Experimental
Luc Leybaert, Maarten A. J. De Smet, Alessio Lissoni, Rosalie Allewaert, H. Llewelyn Roderick, Geert Bultynck, Mario Delmar, Karin R. Sipido, Katja Witschas
Summary: This paragraph mainly discusses the role of connexins in cardiac function. Connexins form hemichannels and gap junctions, and gap junctions are responsible for transmitting electrical and chemical signals between myocardial cells and specialized conduction system cells to synchronize the cardiac cycle and control cardiac pump function. Under pathological conditions, gap junctions close and hemichannels open, leading to disruption of cardiac function and homeostasis. Current evidence shows that hemichannels play an emerging role in myocardial ischemia and arrhythmia, and there are now tools available to selectively inhibit hemichannels without inhibiting gap junctions, as well as to stimulate the incorporation of hemichannels into gap junctions. We review experimental evidence for the contribution of hemichannels to pro-arrhythmic events in ventricular and atrial cardiomyocytes, and link these findings to the molecular control of connexin-43-based hemichannel opening. We conclude that a double-edged approach of both preventing hemichannel opening and preserving gap junctional function will be crucial for further research and development of new connexin-based experimental approaches for treating heart disease.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Immunology
Julika Neumann, Erika Van Nieuwenhove, Lara E. Terry, Frederik Staels, Taylor R. Knebel, Kirsten Welkenhuyzen, Kourosh Ahmadzadeh, Mariah R. Baker, Margaux Gerbaux, Mathijs Willemsen, John S. Barber, Irina I. Serysheva, Liesbeth De Waele, Francois Vermeulen, Susan Schlenner, Isabelle Meyts, David Yule, Geert Bultynck, Rik Schrijvers, Stephanie Humblet-Baron, Adrian Liston
Summary: Calcium signaling is crucial for lymphocyte activation, and disruptions of store-operated calcium entry can lead to severe immunodeficiency. In this study, genetic variations of the ITPR3 gene were identified in two Caucasian patients with immunodeficiency, indicating a potential link between these variations and impaired immune responses. The findings demonstrate the functional connection between defective endoplasmic reticulum calcium channels and immunodeficiency, highlighting the importance of IP(3)Rs as diagnostic targets for patients with specific inborn errors of immunity.
CELLULAR & MOLECULAR IMMUNOLOGY
(2023)
Correction
Immunology
Julika Neumann, Erika Van Nieuwenhove, Lara E. Terry, Frederik Staels, Taylor R. Knebel, Kirsten Welkenhuyzen, Kourosh Ahmadzadeh, Mariah R. Baker, Margaux Gerbaux, Mathijs Willemsen, John S. Barber, Irina I. Serysheva, Liesbeth De Waele, Francois Vermeulen, Susan Schlenner, Isabelle Meyts, David I. Yule, Geert Bultynck, Rik Schrijvers, Stephanie Humblet-Baron, Adrian Liston
CELLULAR & MOLECULAR IMMUNOLOGY
(2023)
