Article
Chemistry, Multidisciplinary
Masanori Nagao, Takeshi Uemura, Tasuku Horiuchi, Yu Hoshino, Yoshiko Miura
Summary: The study demonstrates a screening of glycopolymers for the carbohydrate module method by combining PET-RAFT polymerization and SPRI, achieving a rapid and convenient screening of synthetic glycomimetics, with the optimal glycopolymer structure as a GM1 mimetic strongly interacting with the cholera toxin B subunit.
CHEMICAL COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Samar K. Alselehdar, Monami Chakraborty, Suman Chowdhury, Roy N. Alcalay, Matthew Surface, Robert Ledeen
Summary: The study shows that GM1 ganglioside levels are lower in PD patients, especially in PBMCs, which could potentially apply to early and developing stages of the disease. These findings suggest new directions for future research and disease treatment in PD patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Stefanie S. Schmieder, Raju Tatituri, Michael Anderson, Kate Kelly, Wayne I. Lencer
Summary: This study investigates how the acyl chain structures of complex sphingolipids influence their secretion and intracellular distribution, and finds that lysosomal sorting is achieved by excluding the endocytic pathway sorting tubules. Additionally, cholesterol and unsaturation of the acyl chains also impact the sorting of sphingolipids.
Article
Medicine, Research & Experimental
Xiaofan Jia, Yan Zhang, Ting Wang, Yuan Fu
Summary: A novel cell biology tool was developed to deliver recombinant proteins into mammalian cells with high efficiency and selectivity for ganglioside-rich cells. The method hijacked intracellular transport routes of cholera toxin and utilized split intein for protein delivery.
MOLECULAR PHARMACEUTICS
(2021)
Article
Biophysics
Maria J. Sarmento, Michael C. Owen, Joana C. Ricardo, Barbora Chmelova, David Davidovic, Ilya Mikhalyov, Natalia Gretskaya, Martin Hof, Mariana Amaro, Robert Vacha, Radek Sachl
Summary: This study investigates the role of ganglioside headgroups in the nanoscale organization and segregation of gangliosides. It demonstrates that the headgroup plays a key role in self-assembly and clustering of gangliosides through hydrogen bonding interactions. The findings provide insight into the physicochemical factors that drive the nanoscopic segregation of gangliosides.
BIOPHYSICAL JOURNAL
(2021)
Review
Biochemistry & Molecular Biology
Giulia Lunghi, Maria Fazzari, Maria Grazia Ciampa, Laura Mauri, Erika Di Biase, Elena Chiricozzi, Sandro Sonnino
Summary: This review focuses on the interactions between gangliosides GM1 and GM3 and protein receptors, highlighting their crucial role in controlling cell signaling and pathophysiological cellular states.
Article
Pharmacology & Pharmacy
Charles Finsterwald, Sara Dias, Pierre J. Magistretti, Sylvain Lengacher
Summary: Ganglioside GM1 exerts its metabolic and neuroprotective effects by promoting glycolysis in astrocytes, enhancing neuronal mitochondrial activity, and triggering the expression of neuroprotection genes when neurons are cultured in the presence of astrocytes.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Jay S. S. Schneider
Summary: Parkinson's disease is a progressive neurodegenerative disorder impacting millions of patients worldwide. While there are treatments available for symptoms, there is no proven therapy to slow or halt disease progression. The failure of disease-modifying agents in clinical trials can be attributed to factors such as patient selection and trial design. Additionally, treatment choices have not adequately addressed the multiple and complex pathogenic mechanisms involved in Parkinson's disease. This paper suggests that using multi-functional therapeutics, such as GM1 ganglioside, which target multiple pathogenic mechanisms, may be a promising alternative strategy for success.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Xiaotong Wang, Rui Zhou, Xiaqin Sun, Jun Li, Jinxin Wang, Weihua Yue, Lifang Wang, Hesheng Liu, Yigong Shi, Dai Zhang
Summary: This study reveals the mechanism of GM1 in Aβ generation and provides evidence that decreasing GM1 levels represents a potential strategy in AD treatment. GM1 can lead to conformational change in the structure of γ-secretase and accelerate the cleavage of APP, leading to reduced plaque deposition and improved cognitive dysfunction in AD.
Article
Immunology
Rajitha Charla, Priyanka P. P. Patil, Vishal S. S. Patil, Vishwambhar V. V. Bhandare, Veeresh Karoshi, Venkanna Balaganur, Rajesh K. K. Joshi, Darasaguppe R. R. Harish, Subarna Roy
Summary: This study investigated the inhibitory activity of polyphenolic compounds from three Indian plants against cholera toxin. Molecular modelling, in vitro and in vivo experiments were carried out, and it was found that Ellagic acid and Chlorogenic acid exhibited significant inhibitory activity against the toxin.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Article
Food Science & Technology
Donghyun Lee, Hunseok Choi, Seonghyeon Son, Jonghyun Bae, Jayun Joo, Dong Wook Kim, Eun Jin Kim
Summary: The expression of virulence genes in Vibrio cholerae is regulated by the ToxR regulon, which is triggered by environmental stimuli during infection in the human small intestine. This study investigates the induction of virulence gene expression under laboratory culture conditions through two point mutations in the toxT gene. The findings suggest that the regulation of virulence gene expression may be more complex than previously thought, involving factors beyond the ToxR regulon.
Article
Microbiology
Johanna Detzner, Charlotte Puettmann, Gottfried Pohlentz, Johannes Muething
Summary: Research has shown that the pentamer of B subunits (choleragenoid) of the cholera toxin has high affinity for the ganglioside GM1, however, the exact structures of GM1 lipoforms have not been fully described in primary human colon epithelial cells; Experiments have revealed the desialylation of GD1a and GT1b by the neuraminidase of V. cholerae, leading to the identification of GM1 species with stable sphingosine and varying fatty acyl chains.
Article
Neurosciences
Takahiro Fuchigami, Yutaka Itokazu, John C. C. Morgan, Robert K. K. Yu
Summary: Parkinson's disease (PD) is a common neurodegenerative disorder that affects the body and mind of millions of people worldwide. The disease is characterized by motor symptoms such as bradykinesia, rigidity, and tremor, as well as non-motor symptoms including loss of smell, sleep disturbances, depression, anxiety, and cognitive impairment. This study found that intranasal infusion of ganglioside GD3 can restore impaired neurogenesis and promote the self-renewal ability of neural stem cells (NSCs) in PD mice, while intranasal infusion of ganglioside GM1 can promote neurogenesis in the adult brain. The combination of GD3 and GM1 has the potential to slow down disease progression and rescue dysfunctional neurons in neurodegenerative brains.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Multidisciplinary Sciences
Elena -Sofia Heinl, Sebastian Lorenz, Barbara Schmidt, Nouf Nasser M. Laqtom, Joseph R. Mazzulli, Laetitia Francelle, Timothy W. Yu, Benjamin Greenberg, Stephan Storch, Ines Tegtmeier, Helga Othmen, Katja Maurer, Malin Steinfurth, Ralph Witzgall, Vladimir Milenkovic, Christian H. Wetzel, Markus Reichold
Summary: The study found that CLN7 may be involved in the infection process of the SARS-CoV-2 virus. CLN7 deficiency leads to a significant reduction in viral load, while overexpression of CLN7 increases viral load. This research provides a potential target for drug development against COVID-19 and helps us understand the physiological function of CLN7.
Article
Immunology
Tuhina Banerjee, Aby Grabon, Michael Taylor, Ken Teter, Denise Monack
Summary: Cholera toxin activates the stimulatory alpha subunit of G protein through ADP-ribosylation, leading to a cytopathic effect by stimulating adenylate cyclase and cAMP production. The toxin triggers the unfolded protein response (UPR), but the process is not directly related to the activation of the adenylate cyclase signaling pathway.
INFECTION AND IMMUNITY
(2021)
Article
Biochemistry & Molecular Biology
Matus Sotak, Meenu Rohini Rajan, Madison Clark, Christina Biorserud, Ville Wallenius, Carolina E. Hagberg, Emma Borgeson
Summary: This study evaluated the status of extracellular matrix (ECM) in metabolically healthy lean (MHL) and metabolically unhealthy obese (MUO) individuals. The results showed that MHL individuals had abundant ECM deposition with high expression of ECM remodeling proteins. In contrast, MUO individuals had lower expression of ECM components but elevated levels of ECM cross-linking and adhesion proteins.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Nutrition & Dietetics
Erik Elebring, Ville Wallenius, Anna Casselbrant, Neil G. Docherty, Carel W. le Roux, Hanns-Ulrich Marschall, Lars Fandriks
Summary: This study aimed to investigate the effects of diets enriched in fat or carbohydrates on glucose absorption in the healthy jejunum and the underlying mechanisms. The results showed that a fat-enriched diet decreased jejunal glucose absorption through a ketogenesis-induced alteration of histone acetylation. This research provides important insights into the metabolic effects of different diets.
Article
Medicine, General & Internal
Gudrun Hoskuldsdottir, My Engstrom, Araz Rawshani, Frida Lener, Ville Wallenius, Lars Fandriks, Karin Mossberg, Bjorn Eliasson
Summary: This study compared the long-term effects and complications of medical treatment and bariatric surgery for obesity. The results showed that bariatric surgery by Roux-en-Y gastric bypass or sleeve gastrectomy was most effective, but significant weight loss could also be achieved through medical treatment with strict caloric restriction. All treatments had positive effects on well-being, cardiovascular risk factors, and levels of vitamins and minerals at the 2-year follow-up, and the safety profiles were similar.
Article
Multidisciplinary Sciences
Elodie Picarda, Phillip M. Galbo, Haihong Zong, Meenu Rohini Rajan, Ville Wallenius, Deyou Zheng, Emma Borgeson, Rajat Singh, Jeffrey Pessin, Xingxing Zang
Summary: The immune checkpoint B7-H3 has been studied in the tumor microenvironment and immunotherapy, but its potential role in metabolism remains largely unknown. This study reveals that B7-H3 is highly expressed in adipose tissue, particularly in adipocyte progenitor cells, and it regulates the glycolytic and mitochondrial activity of these cells. Loss of B7-H3 leads to impaired oxidative metabolism and increased lipid accumulation in derived adipocytes. Knockout of B7-H3 in mice results in spontaneous obesity, metabolic dysfunction, and adipose tissue inflammation.
Article
Dentistry, Oral Surgery & Medicine
Negin Taghat, Peter Lingstrom, Karin Mossberg, Lars Fandriks, Bjorn Eliasson, Anna-Lena Ostberg
Summary: This study found a correlation between obesity and poor oral health, with higher caries levels in obese women. Dental plaque and gingivitis were also found to be high.
ACTA ODONTOLOGICA SCANDINAVICA
(2022)
Article
Multidisciplinary Sciences
Ala Mejaddam, Emily Krantz, Gudrun Hoskuldsdottir, Lars Fandriks, Karin Mossberg, Bjorn Eliasson, Penelope Trimpou, Kerstin Landin-Wilhelmsen
Summary: People with obesity seeking help with weight reduction have lower physical and mental self-reported health-related quality of life (HRQoL) compared to the general population, especially in terms of physical and social functioning, vitality, and general and mental health.
Article
Nutrition & Dietetics
Anna Casselbrant, Ville Wallenius, Erik Elebring, Hanns-Ulrich Marschall, Bengt R. Johansson, Herbert F. Helander, Lars Fandriks
Summary: This study compared the effects of a high-carbohydrate diet and a high-fat diet on the jejunum in healthy individuals. The results showed that the diets led to morphometric changes in the jejunal mucosa and affected the structure and function of mitochondria.
Article
Oncology
Elin M. V. Forsberg, Rebecca Riise, Sara Saellstrom, Joakim Karlsson, Samuel Alsen, Valentina Bucher, Akseli E. Hemminki, Roger Olofsson Bagge, Lars Ny, Lisa M. Nilsson, Henrik Ronnberg, Jonas A. Nilsson
Summary: CAR-T cells equipped with a claw can be used to kill cancer cells. In this study, researchers modified immune cells called tumor-infiltrating lymphocytes to carry the claw, creating CAR-TILs. They found that CAR-TILs can kill melanoma cells in culture and in mice, and they also demonstrated the safety and effectiveness of CAR-TILs in companion dogs with cancer.
Article
Biochemistry & Molecular Biology
Anyelo Duran, David A. Priestman, Macarena Las Heras, Boris Rebolledo-Jaramillo, Valeria Olguin, Juan F. Calderon, Silvana Zanlungo, Jaime Gutierrez, Frances M. Platt, Andres D. Klein
Summary: Using a systems genetics approach, we identified 30 shared predicted modifier genes between hepatic lysosomal enzymes and glycosphingolipids (GSLs), clustered in three pathways and associated with other diseases. Surprisingly, these genes are regulated by ten common transcription factors and miRNA-340p. These findings suggest novel therapeutic targets for Lysosomal Storage Disorders (LSDs) and indicate the potential involvement of GSL metabolism in other pathologies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Endocrinology & Metabolism
Erik Elebring, Anna Casselbrant, Sara M. T. Persson, Lars Fandriks, Ville Wallenius
Summary: Ingestion of nutrients stimulates the secretion of incretins, such as GLP-1, which regulate postprandial insulin release and satiety. This study investigated the inhibitory effect of beta HB on glucose-induced GLP-1 secretion using cell cultures. The results showed that beta HB significantly inhibited GLP-1 secretion in both murine GLUTag cells and differentiated human jejunal enteroid monolayers. The findings suggest that beta HB may act through multiple downstream mediators to regulate GLP-1 secretion.
JOURNAL OF MOLECULAR ENDOCRINOLOGY
(2023)
Article
Cardiac & Cardiovascular Systems
Frida Lener, Gudrun Hoskuldsdottir, Kerstin Landin-Wilhelmsen, Cecilia Bjorkelund, Bjorn Eliasson, Lars Fandriks, Ville Wallenius, My Engstrom, Karin Mossberg
Summary: This study investigated the relationship between nutritional deficiencies and anaemia in patients who reported use of supplementation two years after bariatric surgery versus patients who do not. The results indicated that iron deficiency or anaemia may not be prevented by substitutional treatment per current guidelines after bariatric surgery and highlights there is reason to ensure adequate preoperative micronutrient levels.
NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES
(2023)
Article
Biochemistry & Molecular Biology
Antonino Puglisi, Noemi Bognanni, Graziella Vecchio, Ece Bayir, Peter van Oostrum, Dawn Shepherd, Frances Platt, Erik Reimhult
Summary: Core-shell superparamagnetic iron oxide nanoparticles have great potential as a therapeutic and diagnostic platform in biological systems. This study investigates the biological effects of multifunctional cyclodextrin-appended SPIONs (CySPION) in mutant Npc1-deficient CHO cells. The results show that CySPIONs have low cytotoxicity, are strongly endocytosed, and localized in the lysosomal compartment. The pH-sensitive chemistry of these nanoparticles allows for the release of monomeric cyclodextrins, promoting the removal of accumulated cholesterol. Additionally, CySPIONs demonstrate high transport across blood-brain barrier models, suggesting their potential as a therapeutic approach for cholesterol-related brain diseases.
Article
Biochemistry & Molecular Biology
Akshi Singla, Andrew Boucher, Kerri-Lee Wallom, Michael Lebens, Jennifer J. Kohler, Frances M. Platt, Ulf Yrlid
Summary: Prior research on cholera toxin (CT) binding and intoxication has relied on human colonic cancer derived epithelial cells. However, this study used human enteroids derived from jejunal biopsies to study CT binding and intoxication of human non-transformed small intestinal epithelial cells. The study found that inhibition of fucosylation or O-glycosylation sensitized enteroids to CT intoxication. Furthermore, simultaneous inhibition of fucosylation and O-glycosylation increased the availability of additional glycoconjugates, but counteracted the sensitization in CT intoxication caused by inhibiting O-glycosylation due to reduction in fucose. This suggests a dual role of fucose in influencing CT binding and intoxication. Additionally, the study revealed a role for human genetic variation in determining sensitivity to CT.