Article
Medicine, Research & Experimental
Nicole Muschol, Anja Koehn, Katharina von Cossel, Ilyas Okur, Fatih Ezgu, Paul Harmatz, Maria J. de Castro Lopez, Maria Luz Couce, Shuan-Pei Lin, Spyros Batzios, Maureen Cleary, Martha Solano, Igor Nestrasil, Brian Kaufman, Adam J. Shaywitz, Stephen M. Maricich, Bernice Kuca, Joseph Kovalchin, Eric Zanelli
Summary: This study found that intracerebroventricular administration of tralesinidase alfa can effectively treat Sanfilippo type B and normalize HS and HS-NRE levels in brain tissues. This treatment also reduces hepatomegaly and improves cognitive development in patients.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Multidisciplinary Sciences
Maria Alvarez-Vergara, Alicia E. Rosales-Nieves, Rosana March-Diaz, Guiomar Rodriguez-Perinan, Nieves Lara-Urena, Clara Ortega-de San Luis, Manuel A. Sanchez-Garcia, Miguel Martin-Bornez, Pedro Gomez-Galvez, Pablo Vicente-Munuera, Beatriz Fernandez-Gomez, Miguel A. Marchena, Andrea S. Bullones-Bolanos, Jose C. Davila, Rocio Gonzalez-Martinez, Jose L. Trillo-Contreras, Ana C. Sanchez-Hidalgo, Raquel del Toro, Francisco G. Scholl, Eloisa Herrera, Martin Trepel, Jakob Koerbelin, Luis M. Escudero, Javier Villadiego, Miriam Echevarria, Fernando de Castro, Antonia Gutierrez, Alberto Rabano, Javier Vitorica, Alberto Pascual
Summary: This study demonstrates that Aβ plaques in the brains of AD patients are hubs of endothelial disassembly that induce non-productive angiogenesis, a process aided by microglia and unchained by reduced presenilin function.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Vaishali N. Patel, Dallas L. Pineda, Elsa Berenstein, Belinda R. Hauser, Sophie Choi, Michaela Prochazkova, Changyu Zheng, Corinne M. Goldsmith, Toin H. van Kuppevelt, Ashok Kulkarni, Yuefan Song, Robert J. Linhardt, Alejandro M. Chibly, Matthew P. Hoffman
Summary: Heparan sulfate 3-O-sulfotransferases generate highly sulfated rare heparan sulfate epitopes, and their knockout affects epithelial morphogenesis and salivary gland function.
Article
Biochemistry & Molecular Biology
Zuopeng Wu, Rebecca A. Sweet, Gerard F. Hoyne, Charmaine J. Simeonovic, Christopher R. Parish
Summary: It has been accepted for decades that T lymphocytes and metastasising tumour cells traverse basement membranes (BM) by deploying a battery of degradative enzymes, particularly proteases. However, recent studies suggest that there are other mechanisms that allow cell migration through basement membranes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
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
Developmental Biology
Chenqi Tao, Neoklis Makrides, Jen-Zen Chuang, Yihua Wu, Steven E. Brooks, Jeffrey D. Esko, Ching-Hwa Sung, Xin Zhang
Summary: The study demonstrates the essential role of glycosaminoglycans in retinal angiogenesis, blood vessel pruning, and establishment of the basement membrane. The absence of heparan sulfate affects VEGF signaling, disrupts retinal inner limiting membrane assembly, and increases retinal permeability.
Article
Virology
Ghadah A. Karasneh, Divya Kapoor, Navya Bellamkonda, Chandrashekhar D. Patil, Deepak Shukla
Summary: The increased levels of HPSE can reduce syncytial plaque formation and promote viral egress and release. Transiently enhanced expression of HPSE does not affect HSV-1 entry into cells but facilitates extracellular release of mature virions.
Article
Microbiology
Maitrayee Chatterjee, Liane Z. X. L. Huang, Anna Mykytyn, Chunyan Wang, Mart B. Lamers, Bart Westendorp, Richard B. Wubbolts, Jos P. M. van Putten, Berend-Jan B. Bosch, Bart Haagmans, Karin B. Strijbis
Summary: In this study, the role of host mucins and mucin glycans on SARS-CoV-2 entry into airway epithelial cells was investigated. The removal of mucins from the surface of cells increased the binding of the virus and enhanced infection. This study demonstrates the important role of glycosylated extracellular mucin domains in the entry of SARS-CoV-2.
Review
Biochemistry & Molecular Biology
Anastasia V. Strokotova, Elvira V. Grigorieva
Summary: Glucocorticoids are commonly used to treat various diseases but can cause side effects. Recent studies suggest that the toxic effects of glucocorticoids on key extracellular components in the brain may be an underlying mechanism for these side effects.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Physical
Haiyi Chen, Yu Kang, Mojie Duan, Tingjun Hou
Summary: The study revealed that the presence of heparan sulfate is crucial for the binding between the spike protein of SARS-CoV-2 and host ACE2, while the stability of the T470-F490 loop and hydrophobic interactions play key roles in the binding process.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2021)
Article
Biochemistry & Molecular Biology
Elena Carava, Paola Moretto, Ilaria Caon, Arianna Parnigoni, Alberto Passi, Evgenia Karousou, Davide Vigetti, Jessica Canino, Ilaria Canobbio, Manuela Viola
Summary: Cardiovascular diseases result from various risk factors, and inflammation induced by cytokines like TNF-alpha may lead to changes in vessel matrix composition without affecting cell proliferation or migration.
Article
Immunology
Qi Zhang, Shanshan Pei, Zheyi Zhou, Zhanhang Wang, Yu Peng, Jinyu Chen, Honghao Wang
Summary: The study found that serum and cerebrospinal fluid levels of shed HS and HA were significantly elevated in NMO, MS, and autoimmune GFAP astrocytopathy patients, and correlated with disease severity, indicating potential diagnostic value. These findings suggest glycocalyx degradation and inflammation in these diseases, with increased shedding of HS or HA indicating a worse clinical situation. Therapeutic strategies that protect glycocalyx may be effective in treating these diseases.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Dmitry K. Sokolov, Oleg B. Shevelev, Anna S. Khotskina, Alexandra Y. Tsidulko, Anastasia V. Strokotova, Galina M. Kazanskaya, Alexander M. Volkov, Evgenii E. Kliver, Svetlana V. Aidagulova, Evgenii L. Zavjalov, Elvira V. Grigorieva
Summary: Glioblastoma (GB) is an aggressive cancer with a high chance of recurrence, and the effects of chemotherapy drugs on heparan sulfate (HS) in brain tissue are still unknown.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Anthony J. J. Hayes, James Melrose
Summary: Heparan sulfate is a complex glycosaminoglycan that plays important roles in various biological processes through interactions with extracellular ligands and cellular receptors. Its chain lengths and sequences can vary, providing structural diversity. Heparan sulfate has regulatory properties in tissue development, wound healing, immune regulation, inflammation, and tumor development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Prashant Jain, Chethan D. Shanthamurthy, Shani Leviatan Ben-Arye, Robert J. Woods, Raghavendra Kikkeri, Vered Padler-Karavani
Summary: Selective inhibition of chemokines using structurally defined heparan sulfate oligosaccharides can provide insights into cancer cell migration and metastasis. Rational design and synthesis of N-unsubstituted and N-acetylated heparan sulfate tetrasaccharides have shown selective inhibition of structurally homologous chemokines.
Article
Biochemistry & Molecular Biology
Takashi Ohgita, Yuki Takechi-Haraya, Keisuke Okada, Saki Matsui, Misaki Takeuchi, Chihiro Saito, Kazuchika Nishitsuji, Kenji Uchimura, Ryuji Kawano, Koki Hasegawa, Kumiko Sakai-Kato, Kenichi Akaji, Ken-ichi Izutsu, Hiroyuki Saito
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2020)
Article
Multidisciplinary Sciences
Naoyuki Iwahashi, Midori Ikezaki, Taro Nishikawa, Norihiro Namba, Takashi Ohgita, Hiroyuki Saito, Yoshito Ihara, Toshinori Shimanouchi, Kazuhiko Ino, Kenji Uchimura, Kazuchika Nishitsuji
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Chemistry, Multidisciplinary
Liwei Jiang, Sungwook Jung, Jing Zhao, Vivek Kasinath, Takaharu Ichimura, John Joseph, Paolo Fiorina, Andrew S. Liss, Khalid Shah, Nasim Annabi, Nitin Joshi, Tomoya O. Akama, Jonathan S. Bromberg, Motohiro Kobayashi, Kenji Uchimura, Reza Abdi
Summary: The newly developed MHA112-Taxol drug delivery platform can simultaneously target tumors, TDLNs, and metastatic lesions, effectively reducing the size of primary tumors and the number of metastatic lesions.
Article
Cell Biology
Hitomi Hoshino, Tomoya O. Akama, Kenji Uchimura, Mana Fukushima, Akifumi Muramoto, Takeshi Uehara, Yasuni Nakanuma, Motohiro Kobayashi
Summary: This study demonstrates the expression of distinct sulfated glycans in the cytoplasm and apical membrane of cells in large-sized ducts and ductules, with differences observed in various liver diseases and cholangiocarcinoma. The presence of these glycans as a characteristic feature in ductules and their reactive and neoplastic counterparts suggests a potential role in pathological conditions.
JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY
(2021)
Article
Geriatrics & Gerontology
Youngjae Ryu, Misato Iwashita, Wonyoung Lee, Kenji Uchimura, Yoichi Kosodo
Summary: The study examined how aging affects the mechanical properties of brain tissue, particularly focusing on the impact of neural stem cells (NSCs) in differentiating regions of the hippocampus. It found that stiffness in the brain is influenced by the composition of extracellular matrix (ECM), specifically chondroitin sulfate proteoglycans (CSPGs), which can affect postnatal neurogenesis by altering the mechanical environment of the NSC niche.
FRONTIERS IN AGING NEUROSCIENCE
(2021)
Article
Biology
Kibaek Choe, Jieun Moon, Soo Yun Lee, Eunjoo Song, Ju Hee Back, Joo-Hye Song, Young-Min Hyun, Kenji Uchimura, Pilhan Kim
Summary: The migration of T and B cells in lymph nodes involves distinct pathways, with a preference for certain hot spots. Specifically, they tend to choose FRCS covered by CD11c+ dendritic cells as migration sites.
LIFE SCIENCE ALLIANCE
(2021)
Article
Biochemistry & Molecular Biology
Kazuchika Nishitsuji, Midori Ikezaki, Shino Manabe, Kenji Uchimura, Yukishige Ito, Yoshito Ihara
Summary: C-Mannosylation affects the biological functions of proteins, especially in thrombospondin 1 repeats. C-Mannosylated WSPW peptide inhibits TGF-beta-mediated synaptogenesis by suppressing Smad 2 activation. The molecular details of how C-mannosylation affects the biological functions of WxxW motifs require further study for clarification.
GLYCOCONJUGATE JOURNAL
(2022)
Review
Biochemistry & Molecular Biology
Kazuchika Nishitsuji, Kenji Uchimura
Summary: In protein misfolding diseases, sulfated GAGs play a critical role in the pathology of amyloidosis by determining specific interactions between GAGs and their protein ligands.
TRENDS IN GLYCOSCIENCE AND GLYCOTECHNOLOGY
(2021)
Article
Anatomy & Morphology
Yoshiko Takeda-Uchimura, Kazuchika Nishitsuji, Midori Ikezaki, Tomoya O. Akama, Yoshito Ihara, Fabrice Allain, Kenji Uchimura
Summary: KS glycan is crucially attached to proteoglycans in the adult brain. Beta3Gn-T7, encoded by B3gnt7, is identified as a major enzyme for KS synthesis in neuropils and the perineuronal region. This suggests that Beta3Gn-T7 in oligodendrocyte lineage cells may play a significant role in forming neuropils and perineuronal nets in the adult brain.
FRONTIERS IN NEUROANATOMY
(2022)
Article
Biochemistry & Molecular Biology
Kenji Uchimura, Kazuchika Nishitsuji, Li-Ting Chiu, Takashi Ohgita, Hiroyuki Saito, Fabrice Allain, Veeranjaneyulu Gannedi, Chi-Huey Wong, Shang-Cheng Hung
Summary: Misregulation and abnormal processing of amyloidogenic proteins lead to amyloidosis, and the synthesized 6-O-phosphorylated HS/HP oligosaccharides have competitive effects on inhibiting Aβ fibril formation.
Article
Cell Biology
Rana El Masri, Amal Seffouh, Caroline Roelants, Ilham Seffouh, Evelyne Gout, Julien Perard, Fabien Dalonneau, Kazuchika Nishitsuji, Fredrik Noborn, Mahnaz Nikpour, Goran Larson, Yoann Cretinon, Melanie Friedel-Arboleas, Kenji Uchimura, Regis Daniel, Hugues Lortat-Jacob, Odile Filhol, Romain R. Vives
Summary: This study found that human HSulf-2 enzyme carries a chondroitin/dermatan sulfate glycosaminoglycan (GAG) chain, which regulates the enzyme's activity and is promoted by mammalian hyaluronidase.
Article
Biochemistry & Molecular Biology
Yoshiko Takeda-Uchimura, Midori Ikezaki, Tomoya O. Akama, Kaho Nishioka, Yoshito Ihara, Fabrice Allain, Kazuchika Nishitsuji, Kenji Uchimura
Summary: In this study, it was found that CL40-positive sialylated and sulfated glycans are abundant in the pleural mesothelium and are synthesized complementarily by GlcNAc6ST2 and GlcNAc6ST3 under physiological conditions.
Review
Immunology
Bilal Hussain, Vivek Kasinath, Gabriel P. Ashton-Rickardt, Thomas Clancy, Kenji Uchimura, George Tsokos, Reza Abdi
Summary: High endothelial venules (HEVs) are specialized blood vessels that support the migration of lymphocytes. They are formed in organs affected by chronic inflammation and cancer. HEVs play a crucial role in cancer treatment and immunotherapy. This review discusses the characteristics of HEVs, the mechanisms of their formation, HEV-dependent immunotherapies, and the potential use of HEV-targeted therapies in the treatment of cancer and immune-mediated diseases.
TRENDS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Naoyuki Iwahashi, Midori Ikezaki, Yoshihiro Komohara, Yukio Fujiwara, Tomoko Noguchi, Kaho Nishioka, Kazuko Sakai, Kazuto Nishio, Mitsuharu Ueda, Yoshito Ihara, Kenji Uchimura, Kazuhiko Ino, Kazuchika Nishitsuji
Summary: Recent studies have found that aggregates of mutant p53 proteins can propagate and disrupt normal p53 function in cancer cells. This study demonstrates the involvement of p53 aggregate transmission in poor prognosis and chemotherapy resistance in cancer.
Article
Multidisciplinary Sciences
Yuki Takechi-Haraya, Takashi Ohgita, Mana Kotani, Hiroki Kono, Chihiro Saito, Hiroko Tamagaki-Asahina, Kazuchika Nishitsuji, Kenji Uchimura, Takeshi Sato, Ryuji Kawano, Kumiko Sakai-Kato, Ken-ichi Izutsu, Hiroyuki Saito
Summary: By studying the structural isomers of A2-17 peptide, we found a correlation between the hydrophobic moment and membrane interaction and direct cell penetration. A2-17 L14R/R15L, with the highest hydrophobic moment, showed the most efficient penetration into cells, forming stable membrane pores.
SCIENTIFIC REPORTS
(2022)