Article
Biochemistry & Molecular Biology
Takuto Shimizu, Emiko Nogami, Yuka Ito, Kazuo Morikawa, Masaki Nagane, Tadashi Yamashita, Tsuyoshi Ogawa, Fuyuki Kametani, Hisashi Yagi, Naomi Hachiya
Summary: Prion disease is a neurodegenerative disorder with no effective therapeutic agents developed so far.
NEUROCHEMICAL RESEARCH
(2021)
Article
Chemistry, Physical
Siddhartha Banerjee, Divya Baghel, Md Hasan Ul Iqbal, Ayanjeet Ghosh
Summary: Spontaneous aggregation of amyloid beta (Afi) proteins is a key pathological feature of Alzheimer's disease, but the structure of early-stage aggregates is not well understood. This study used atomic force microscopy-infrared nanospectroscopy to investigate the aggregation process of Afi 16-22 and found a structural transition from oligomers with parallel β-sheets to antiparallel fibrils.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2022)
Article
Biochemistry & Molecular Biology
Ruben Gomez-Gutierrez, Ujjayini Ghosh, Wai-Ming Yau, Nazaret Gamez, Katherine Do, Carlos Kramm, Hamid Shirani, Laura Vegas-Gomez, Jonathan Schulz, Ines Moreno-Gonzalez, Antonia Gutierrez, K. Peter R. Nilsson, Robert Tycko, Claudio Soto, Rodrigo Morales
Summary: The study examines the seeding properties of two structurally defined synthetic misfolded Aβ strains (2F and 3F) and their different pathological features, including aggregation rates, plaque formation, tropism to specific brain regions, recruitment of different Aβ peptides, and induction of microglial and astroglial responses. Moreover, the study analyzes the atomic-level characterization of purified Aβ polymorphs and provides relevant information on the pathological significance of misfolded Aβ strains.
Article
Biochemistry & Molecular Biology
Jessica Guillerm, Jean-Marie Frere, Filip Meersman, Andre Matagne
Summary: The study focused on a tandem-repeat protein and showed that it can fold in a highly cooperative manner.
Article
Biophysics
Shaopei Li, Kagan Kerman
Summary: Electrochemical biosensors have been utilized in studying biometal-protein interactions in neurodegenerative diseases such as Alzheimer's and Parkinson's. These sensors have shown promise in monitoring conformational changes induced by biometals and identifying disease biomarkers like amyloid-beta and alpha-synuclein.
BIOSENSORS & BIOELECTRONICS
(2021)
Article
Cell Biology
Nazaret Gamez, Javiera Bravo-Alegria, Yumeng Huang, Nelson Perez-Urrutia, Deepa Dongarwar, Claudio Soto, Rodrigo Morales
Summary: Extensive experimental and human-derived evidence suggests that misfolded A beta particles spread similarly to infectious prions. Administration of A beta seeds accelerates brain amyloidosis. Injection of A beta seeds in the tongue accelerates the appearance of plaques, while extra-nasal exposure increases amyloid pathology in the olfactory bulb. The results suggest that A beta seeds can be transported to the brain by retrograde axonal transport, and research in this direction may be relevant in understanding disease mechanisms, diagnosis, and iatrogenic transmission risk evaluation.
Article
Biotechnology & Applied Microbiology
Akiko Amano, Nobuo Sanjo, Wataru Araki, Yasutaka Anraku, Makoto Nakakido, Etsuro Matsubara, Takami Tomiyama, Tetsuya Nagata, Kouhei Tsumoto, Kazunori Kataoka, Takanori Yokota
Summary: Researchers developed polymeric nanomicelles capable of passing through the blood-brain barrier to deliver specific antibodies to the brain. The administration of 6H4 antibody fragments in polymeric nanomicelles for 10 weeks significantly reduced the amounts of toxic A beta species in the brain and inhibited the formation of A beta plaques. Behavioral analysis also showed an improvement in spatial reference memory in mice with Alzheimer's disease.
JOURNAL OF NANOBIOTECHNOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Diane L. Ritchie, Marcelo A. Barria
Summary: Accumulation and propagation of misfolded proteins in the brain are shared pathological features of many neurodegenerative diseases. While there is no epidemiological evidence suggesting infectiousness in neurodegenerative disorders, experimental models show potential prion-like transmission of other pathogenic proteins. Concerns exist regarding the transmission of misfolded proteins beyond prion protein.
Article
Clinical Neurology
Dovile Poceviciute, Cristina Nunez-Diaz, Bodil Roth, Shorena Janelidze, Andreas Giannisis, Oskar Hansson, Malin Wennstrom
Summary: Alzheimer's disease is characterized by Aβ plaques, NFT, and neuroinflammation, but recent studies suggest that peripheral inflammation might also play a role. This study found that plasma IgA levels were higher in AD patients, especially in APOE ε4 non-carriers, and these levels were associated with cognitive decline and neuropathology. This suggests that the relationship between AD pathology and plasma IgA levels may be influenced by APOE allele status.
ALZHEIMERS RESEARCH & THERAPY
(2022)
Article
Nanoscience & Nanotechnology
Kai Zhou, Yang Liu, Ke Li, Yingfeng Li, Shicao Wei, Yule Zhou, Hong Yu, Yanru Zhang, Jingqi Lv, Botao Xiao, Chao Zhong
Summary: This study investigates the mechanical properties of the CsgA protein and its assembled nanofibers, CsgA-CBD and Mfp5-CsgA. The unfolding spectra of a single CsgA molecule were found to be non-uniform, with several beta-sheets breaking simultaneously under external force. The average persistence lengths and Young's moduli of the nanofibers were also measured. The study provides important insights for the use of CsgA as a biomaterial and the design of nanofibers with tunable functions using mechanochemical coupling.
ACS APPLIED NANO MATERIALS
(2022)
Article
Chemistry, Multidisciplinary
Peng Teng, Mengmeng Zheng, Darrell Cole Cerrato, Yan Shi, Mi Zhou, Songyi Xue, Wei Jiang, Lukasz Wojtas, Li-June Ming, Yong Hu, Jianfeng Cai
Summary: This study demonstrated the solid-state right-handed helical propensity of the 4(13)-helix of L-alpha/L-sulfono-gamma-AA peptides, even as short as 11-mer, using high-resolution X-ray single crystallography. The atomic level folding conformation of the foldamers was elucidated by 2D NMR and circular dichroism, showing that the helical handedness of this class of foldamer is controlled by the chirality of their chiral side chains.
COMMUNICATIONS CHEMISTRY
(2021)
Review
Neurosciences
Alessio Crestini, Francesca Santilli, Stefano Martellucci, Elena Carbone, Maurizio Sorice, Paola Piscopo, Vincenzo Mattei
Summary: Specific protein misfolding and aggregation are mechanisms underlying neurodegenerative diseases such as prion disease and Alzheimer's disease (AD). The misfolded proteins contribute to the pathological features of AD, including the formation of plaques and neurofibrillary tangles. The cellular prion protein (PrPC) has an important role in the pathogenesis of AD.
JOURNAL OF ALZHEIMERS DISEASE
(2022)
Review
Chemistry, Inorganic & Nuclear
Jun Li, Wang Liao, Dongqing Huang, Meitong Ou, Tongkai Chen, Xinlu Wang, Ruiyue Zhao, Lingyan Zhang, Lin Mei, Jun Liu, Ping Luan
Summary: Alzheimer's disease is a common central neurodegenerative disorder characterized by behavioral disturbance and progressive cognitive impairment. Accumulation of soluble oligomers and amyloid plaques outside nerve cells are crucial in its development. Advanced strategies for detecting and modulating amyloid beta (A beta) in diagnosis and treatment include the use of large-scale apparatus and novel devices, as well as therapeutic agents and nanomaterials.
COORDINATION CHEMISTRY REVIEWS
(2023)
Review
Pharmacology & Pharmacy
Satyam Pati, Avtar Singh Gautam, Mangaldeep Dey, Aman Tiwari, Rakesh Kumar Singh
Summary: Inflammation and cell death processes controlled by RIPK1 play a crucial role in maintaining organ homeostasis. Inhibiting RIPK1 has shown promising effects in preventing neuronal cell death, leading to a potential reduction in neurodegeneration and neuroinflammation. Therefore, RIPK1 has emerged as an important therapeutic target for Alzheimer's disease.
DRUG DISCOVERY TODAY
(2023)
Article
Biochemistry & Molecular Biology
Maria Elisabetta Clementi, Beatrice Sampaolese, Gabriele Di Sante, Francesco Ria, Rosa Di Liddo, Vincenzo Romano Spica, Fabrizio Michetti
Summary: The study demonstrated that the expression of S100B in astrocytoma cells plays a crucial role in the activation of reactive astrocytic processes, including cytotoxicity, ROS and NOS activation. Silencing S100B in astrocytoma cells effectively protected the cells from amyloid beta-peptide-induced damage, reducing cell death, oxygen radical generation and nitric oxide synthase activity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Infectious Diseases
Motohiko Ogawa, Yoshitaka Shirasago, Isei Tanida, Soichiro Kakuta, Yasuo Uchiyama, Masayuki Shimojima, Kentaro Hanada, Masayuki Saijo, Masayoshi Fukasawa
Summary: The o-dihydroxybenzene backbone in caffeic acid and its analogs is crucial for their anti-SFTSV activity. Modifying this backbone with various residues may enhance the antiviral effect against SFTSV.
JOURNAL OF INFECTION AND CHEMOTHERAPY
(2021)
Article
Biochemistry & Molecular Biology
Riccardo Rizzo, Domenico Russo, Kazuo Kurokawa, Pranoy Sahu, Bernadette Lombardi, Domenico Supino, Mikhail A. Zhukovsky, Anthony Vocat, Prathyush Pothukuchi, Vidya Kunnathully, Laura Capolupo, Gaelle Boncompain, Carlo Vitagliano, Federica Zito Marino, Gabriella Aquino, Daniela Montariello, Petra Henklein, Luigi Mandrich, Gerardo Botti, Henrik Clausen, Ulla Mandel, Toshiyuki Yamaji, Kentaro Hanada, Alfredo Budillon, Franck Perez, Seetharaman Parashuraman, Yusuf A. Hannun, Akihiko Nakano, Daniela Corda, Giovanni D'Angelo, Alberto Luini
Summary: Research shows that a group of sequentially-acting enzymes in the Golgi bind to the oncogenic protein GOLPH3, affecting glycosphingolipid synthesis and cell proliferation by regulating enzyme localization and degradation rate. These findings reveal a novel oncogenic mechanism of action for GOLPH3 in glycosphingolipid metabolism.
Article
Biochemistry & Molecular Biology
Chisato Sakuma, Tsuyoshi Sekizuka, Makoto Kuroda, Kentaro Hanada, Toshiyuki Yamaji
Summary: Screening in African green monkey cells identified SYS1 as a crucial gene for STx-induced cell death, impacting glycan biosynthesis through regulation of intra-Golgi and endosome-TGN retrograde transports. This indicates the applicability of the human CRISPR KO library in Vero cell lines.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Yuko Okemoto-Nakamura, Kenji Someya, Toshiyuki Yamaji, Kyoko Saito, Makoto Takeda, Kentaro Hanada
Summary: Polio, caused by poliovirus, is a disabling and life-threatening disease. Despite successful global vaccination efforts eradicating serotypes 2 and 3, vaccine-derived poliovirus remains a serious issue. The World Health Organization is working on a Global Action Plan for the global eradication of polio, emphasizing stringent control of potentially PV-infected materials.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Kyoko Furuita, Marina Hiraoka, Kentaro Hanada, Toshimichi Fujiwara, Chojiro Kojima
Summary: The study found that the major sperm protein domain of VAP binds specifically to peptides containing FFAT-like motifs, contributing to the discovery of new VAP interactors. Additionally, the RNA-dependent RNA polymerase of SARS-CoV-2 also contains an FFAT-like motif that binds specifically to VAP-A(MSP) and other FFAT-like motifs.
Article
Microbiology
Atsushi Yamanaka, Mami Matsuda, Tamaki Okabayashi, Pannamthip Pitaksajjakul, Pongrama Ramasoota, Kyoko Saito, Masayoshi Fukasawa, Kentaro Hanada, Tomokazu Matsuura, Masamichi Muramatsu, Tatsuo Shioda, Ryosuke Suzuki
Summary: Thailand is a highly endemic country for flavivirus infections, and a study using neutralization tests on samples from healthy donors in four regions revealed that dengue virus types 1 and 2, as well as Zika virus, are the predominant circulating flaviviruses in Thailand, with varying prevalence of Japanese encephalitis virus in different regions. The findings suggest sustained circulation of Zika virus in Thailand since before 2012, highlighting the importance of understanding the distribution of different flaviviruses for public health purposes.
Article
Biochemical Research Methods
Toshihiko Sugiki, Young-Ho Lee, Nesreen Alsanousi, Kaito Murata, Izuru Kawamura, Toshimichi Fujiwara, Kentaro Hanada, Chojiro Kojima
Summary: In this study, we demonstrated that a specific interaction between the pleckstrin homology (PH) domain of ceramide transport protein (CERT) and phosphatidylinositol 4-monophosphate (PI4P) can be detected using structural and thermodynamic analyses. This interaction can be distinguished from nonspecific interactions with the bulk surface of the lipid nanodisc. Our NMR-ITC hybrid strategy provides detailed characterization of protein-lipid membrane interactions.
ANALYTICAL BIOCHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Norito Tamura, Shota Sakai, Loreto Martorell, Roser Colome, Aya Mizuike, Asako Goto, Juan Dario Ortigoza-Escobar, Kentaro Hanada
Summary: Genetic mutations in CERT1 may lead to intellectual disability by affecting sphingolipid metabolism and neural development, resulting in abnormal brain function.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Kentaro Shimasaki, Keigo Kumagai, Shota Sakai, Toshiyuki Yamaji, Kentaro Hanada
Summary: This study reveals that hyperosmotic stress induces the phosphorylation of CERT at serine 315 residue without affecting the phosphorylation state of the serine-repeat motif. The enhanced binding of CERT with VAP-A in a phosphorylation-dependent manner occurs throughout the ER under hyperosmotic conditions. Additionally, de novo synthesis of sphingomyelin with very-long acyl chains is found to increase through a CERT-independent mechanism under hyperosmotic stress.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Kentaro Hanada, Shota Sakai, Keigo Kumagai
Summary: This article explains the significance of lipid transfer proteins (LTPs) and the recent developments in the use of inhibitors for medicinal research.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Jun Kobayashi, Minetaro Arita, Shota Sakai, Hirotatsu Kojima, Miki Senda, Toshiya Senda, Kentaro Hanada, Ryuichi Kato
Summary: Oxysterol-binding protein (OSBP), as a conserved host factor, transports cholesterol and phosphatidylinositol 4-monophosphate (PtdIns[4]P) between different organelles, and serves as a factor for the replication of various viruses. In this study, the crystal structure of the lipid transfer domain of human OSBP in complex with endogenous cholesterol was determined, revealing the interaction between cholesterol and the hydrophobic tunnel of OSBP. Mutagenesis analysis identified specific amino acid residues required for viral replication, and the M446W variant showed tolerance to the OSBP inhibitor T-00127-HEV2, suggesting its potential use in studying the in vivo functions of OSBP.
ACS INFECTIOUS DISEASES
(2022)
Article
Genetics & Heredity
Kazuhiro Konishi, Toshiyuki Yamaji, Chisato Sakuma, Fumio Kasai, Toshinori Endo, Arihiro Kohara, Kentaro Hanada, Naoki Osada
Summary: This study performed a comparative analysis of Vero E6 cell line with other Vero sublines, revealing genetic differences including single nucleotide variants, indels, and copy number variations. The study also identified specific missense variants in Vero E6 that may contribute to its unique response to viral infection compared to other sublines.
FRONTIERS IN GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Asako Goto, Daichi Egawa, Nario Tomishige, Toshiyuki Yamaji, Kentaro Shimasaki, Keigo Kumagai, Kentaro Hanada
Summary: This study identified an unknown cluster of amino acids in CERT that is involved in the regulation of CERT function, and substitutions of these amino acids with alanine can release the inhibitory effect on CERT activity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Virology
Kouacou Konan, Simon Alem Ogbamikael, Eric Yager, Toshiyuki Yamaji, Jennifer Cerone, Meredith Monaco-Brown, Margarida Barroso, Kentaro Hanada
Summary: Zika virus relies on host lipids, specifically glycosphingolipids, for successful replication. Knockout or inhibition of enzymes involved in glycosphingolipid synthesis significantly reduces virus titers and genome replication, while supplementation of glucosylceramide rescues viral replication.
Article
Biochemistry & Molecular Biology
Yoshimi Shimizu, Takehiro Shinoda, Yoshitaka Shirasago, Masuo Kondoh, Naoko Shinya, Kentaro Hanada, Kiyohito Yagi, Tetsuro Suzuki, Takaji Wakita, Tomomi Kimura-Someya, Mikako Shirouzu, Masayoshi Fukasawa
Summary: The study demonstrates that the conversion of monoclonal antibodies to monovalent antigen-binding fragments and single-chain variable fragment antibodies maintains high binding specificity and affinity, and also shows inhibition of HCV infection. These functional monovalent OCLN-binding probes have potential as drug candidates and tools for studies of OCLN in biology and pharmaceuticals.