Article
Biochemistry & Molecular Biology
Isabella Sampaio, Felipe Domingues Quatroni, Paula Maria Pincela Lins, Alessandro S. Nascimento, Valtencir Zucolotto
Summary: This study investigated the effect of ascorbic acid (AA) on amyloid-beta 1-42 (Aβ42) aggregation and revealed the molecular interactions involved. The results showed that AA reduced the fibril content of Aβ42 and prevented the aggregation by binding to specific sites between the beta-strands of Aβ42 oligomers. These findings contribute to the development of accessible therapy for Alzheimer's disease and the design of novel drugs for amyloidogenic diseases.
Article
Biochemistry & Molecular Biology
Rina Nakamura, Toshifumi Akizawa, Motomi Konishi
Summary: We discovered a hydrolytic peptide called JAL-TA9 and modeled its catalytic center using computational simulations. We found that GSGYR and RYGSG peptides may form catalytic triads and oxyanion holes. These peptides can cleave A beta 11-29 and suppress its aggregation, showing similar cleavage positions. This study highlights the importance of Catalytides in understanding structure-activity relationships.
Review
Chemistry, Medicinal
Daniela Malafaia, Helio M. T. Albuquerque, Artur M. S. Silva
Summary: Alzheimer's disease is a common form of dementia in the elderly with no cure currently available. Multi-target compounds show promise in addressing various factors related to AD. Accumulation of Aβ plaques and NFTs are key features of AD, attracting significant research attention for early diagnosis and treatment.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Xingyuan Zou, Sebastian Himbert, Alix Dujardin, Janos Juhasz, Samantha Ros, Harald D. H. Stover, Maikel C. Rheinstadter
Summary: The study found that curcumin and homotaurine can effectively reduce the aggregation of amyloid beta and have no observable impact on brain membranes. These drugs inhibit A beta aggregation by changing membrane properties and binding to A beta peptides. Membrane-lipid therapy may be an effective approach to inhibit peptide aggregation.
ACS CHEMICAL NEUROSCIENCE
(2021)
Article
Chemistry, Analytical
Xueli Wang, Chengke Wang, Hei-Nga Chan, Iyaswamy Ashok, Senthil Kumar Krishnamoorthi, Min Li, Hung-Wing Li, Man Shing Wong
Summary: Novel near infrared emissive fluorophores exhibit strong selectivity towards Aβ oligomers and monomers, good biocompatibility and stability, and significant inhibitory effects on Aβ aggregation.
Article
Biochemistry & Molecular Biology
Katerina Konstantoulea, Patricia Guerreiro, Meine Ramakers, Nikolaos Louros, Liam D. Aubrey, Bert Houben, Emiel Michiels, Matthias De Vleeschouwer, Yulia Lampi, Luis F. Ribeiro, Joris Wit, Wei-Feng Xue, Joost Schymkowitz, Frederic Rousseau
Summary: The study found that proteins enriched in homologous sequences to Aβ aggregation-prone regions are present in Aβ plaques from AD patients, suggesting heterotypic amyloid interactions may occur. These proteins can modify Aβ assembly kinetics, fibril morphology, and deposition pattern in vitro. Additionally, it was discovered that transient expression of three of these proteins in an Aβ reporter cell line promotes Aβ amyloid aggregation, indicating a potential role of heterotypic APR interactions in amyloid-deposition diseases.
Review
Chemistry, Medicinal
Joao P. S. Ferreira, Helio M. T. Albuquerque, Susana M. Cardoso, Artur M. S. Silva, Vera L. M. Silva
Summary: Alzheimer's disease (AD) is a major cause of dementia worldwide, with no disease-modifying treatments currently available. Distinct pharmacological targets like Acetylcholinesterase (AChE) and B-secretase-1 (BACE-1) have been explored for AD treatment. Research is focused on developing multi-target directed ligands as an alternative approach to single-target drugs.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Misato Tajiri, Ryo Yamada, Mayumi Hotsumi, Koki Makabe, Hiroyuki Konno
Summary: This study describes the total synthesis of berberine and selected analogues, and evaluates their effectiveness as amyloid beta (Aβ) aggregation inhibitors. The key step in the synthesis is the assembly of the berberine framework using an intermolecular Heck reaction. Berberine analog 17, incorporating a tertiary amine moiety, demonstrated good anti-Aβ aggregation activity, water solubility, and minimal toxicity to nerve cells.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
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)
Article
Engineering, Biomedical
Bibin Anand, Qi Wu, Maryam Nakhaei-Nejad, Govindarajan Karthivashan, Lyudmyla Dorosh, Sara Amidian, Abhishek Dahal, Xiuju Li, Maria Stepanova, Holger Wille, Fabrizio Giuliani, Satyabrata Kar
Summary: Native PLGA nanoparticles show therapeutic potential in the treatment of Alzheimer's disease by suppressing aggregation of beta-amyloid peptides, triggering their disassembly, reducing phosphorylation of tau protein, enhancing neuronal viability, and attenuating memory deficits and A beta levels in animal models of AD.
BIOACTIVE MATERIALS
(2022)
Article
Biochemistry & Molecular Biology
Panagiotis M. Spatharas, Georgia I. Nasi, Paraskevi L. Tsiolaki, Marilena K. Theodoropoulou, Nikos C. Papandreou, Andreas Hoenger, Ioannis P. Trougakos, Vassiliki A. Iconomidou
Summary: Clusterin is identified as a glycoprotein involved in amyloid formation and has aggregation-prone regions that can form amyloid-like fibrils while also inhibiting amyloid-beta fibril formation. These findings suggest a potential role of clusterin in the molecular mechanism of inhibiting amyloid formation and indicate a possible involvement of molecular chaperones with amyloidogenic properties in regulating amyloid formation.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2022)
Article
Engineering, Chemical
Wei Liu, Xueting Sun, Xiaoyan Dong, Yan Sun
Summary: The chiral influence of peptide inhibitors on Aβ fibrillogenesis and cytotoxicity was investigated in this study. It was found that the D-enantiomer exhibited stronger inhibition effect on Aβ self-assembly compared to the L-enantiomer, with significant differences in their reaction.
CHINESE JOURNAL OF CHEMICAL ENGINEERING
(2022)
Article
Biochemistry & Molecular Biology
Sanaa Sharari, Nishant N. Vaikath, Magdalini Tsakou, Simona S. Ghanem, Kostas Vekrellis
Summary: AD is a common neurodegenerative disorder characterized by memory impairment and cognitive deficits. Currently, there is no proven medication to cure or prevent the disease progression. However, using inhibitors to block the aggregation of Aβ peptide in the CNS shows promise as a therapeutic intervention. Herbal phenolic compounds, such as SA and DMyr, have been shown to inhibit the aggregation and toxicity of Aβ40 and Aβ42, while Gn Rb1 had no effect. These compounds could potentially be used as effective treatments for AD and related disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Analytical
Cen Ding, Changhong Li, Qing Meng, Chengyuan Qian, Changli Zhang, Liu Yang, Xiaohui Wang, Yanqing Wang
Summary: A label-free fluorescent probe (BTS) was reported for dynamic in situ visualization of A beta 40 aggregation. The probe binds to all forms of A beta 40 with high affinity and can monitor the entire A beta aggregation process with high selectivity and sensitivity.
SENSORS AND ACTUATORS B-CHEMICAL
(2021)
Article
Biotechnology & Applied Microbiology
Pallabi Sil Paul, Jae-Young Cho, Qi Wu, Govindarajan Karthivashan, Emily Grabovac, Holger Wille, Mariana Kulka, Satyabrata Kar
Summary: The study found that native PLGA can inhibit the aggregation of A beta peptides and disassemble existing aggregates, protecting neurons from toxicity associated with Alzheimer's disease pathology at temperatures outside the physiological range. These findings support the unique therapeutic potential of PLGA nanoparticles in the treatment of AD.
JOURNAL OF NANOBIOTECHNOLOGY
(2022)
Article
Food Science & Technology
Masahiro Kuragano, Wataru Yoshinari, Xuguang Lin, Keiya Shimamori, Koji Uwai, Kiyotaka Tokuraku
Article
Biochemistry & Molecular Biology
Xuguang Lin, Kenichi Watanabe, Masahiro Kuragano, Yukina Kurotaki, Ushio Nakanishi, Kiyotaka Tokuraku
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Biochemistry & Molecular Biology
Xuguang Lin, Kenichi Watanabe, Masahiro Kuragano, Kiyotaka Tokuraku
Summary: The study found that AEFs extracted and purified from different animal species (camel, cat, cattle, goat, and mouse) could promote mouse SAA protein aggregation in vitro, with mouse and cat AEFs showing higher mSAA aggregation-promoting activity than camel, cattle, and goat AEFs. This suggests that AA amyloidosis exhibits higher transmission activity among animals carrying genetically homologous SAA gene, providing a new understanding of the pathogenesis of amyloidosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Pathology
Xuguang Lin, Masahiro Kuragano, Kenichi Watanabe, Kiyotaka Tokuraku
Summary: The study found that amyloid fibrils from different animal species exhibit similar genetic homology and morphology, despite differences in fibril width and crossover distance. Analysis of amyloid protein and serum amyloid A sequences demonstrated high homology, suggesting similar fibril characteristics across species.
VETERINARY PATHOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Naoki Hosokawa, Masahiro Kuragano, Atsuki Yoshino, Keitaro Shibata, Taro Q. P. Uyeda, Kiyotaka Tokuraku
Summary: The study focuses on the cooperative interaction between fimbrin and actin filaments in forming parallel bundles. It was found that the actin-binding domain of fimbrin promotes the well-ordered arrangement of actin filaments, while its interaction with the glass surface affects bundle formation.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Shinji Matsuzaki, Kento Azuma, Xuguang Lin, Masahiro Kuragano, Koji Uwai, Shinya Yamanaka, Kiyotaka Tokuraku
Summary: The study found that 15-20% water content in Ca(OH)(2) is necessary for disinfection to occur in practice, and the disinfection ability of Ca(OH)(2) decreases within two weeks to one month under actual conditions. Granules prepared from Ca(OH)(2) and zeolite maintain high alkalinity for more than twice as long as calcium powder.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Xian Yu, Xiao Chen, Mamta Amrute-Nayak, Edward Allgeyer, Aite Zhao, Hannah Chenoweth, Marc Clement, James Harrison, Christian Doreth, George Sirinakis, Thomas Krieg, Huiyu Zhou, Hongda Huang, Kiyotaka Tokuraku, Daniel St Johnston, Ziad Mallat, Xuan Li
Summary: Myocardial infarction leads to compromised cardiac function and chronic heart failure, necessitating the development of new drugs to improve cardiomyocyte contractility. Recent research highlights the role of MARK4 in regulating microtubule detyrosination in cardiomyocytes, making it a promising therapeutic target for improving cardiac function post-myocardial infarction.
Article
Chemistry, Multidisciplinary
Motona Matsubara, Hiroyasu Ukai, Masahiro Kuragano, Kiyotaka Tokuraku, Hideyuki Nakano
Summary: Upon irradiation with a polarized laser beam, achiral azobenzene-based molecular glass particles exhibited a wavy string-like morphology in agar gel, with helical structures at their ends showing left-handed screw configuration. This chiral photomechanical behavior was attributed to the different dynamic viscoelasticity between clockwise and counterclockwise rotations of the surrounding agar gel, which was confirmed by the sliding behavior of the gel in a glass tube.
Article
Biophysics
Masahiro Kuragano, Shinya Yamanaka, Kiyotaka Tokuraku
Summary: Abnormal aggregation and accumulation of misfolded proteins are involved in the development of amyloidosis. This study analyzed the process of Aβ aggregates in Alzheimer's disease using real-time 3D imaging. The findings suggest that 40% glycerol solution affects the morphology and aggregation of Aβ fibrils, which is consistent with the symptom progression of Alzheimer's disease.
COLLOIDS AND SURFACES B-BIOINTERFACES
(2022)
Article
Biochemistry & Molecular Biology
Damiana Scuteri, Laura Rombola, Takafumi Hayashi, Chizuko Watanabe, Shinobu Sakurada, Kengo Hamamura, Tsukasa Sakurada, Paolo Tonin, Giacinto Bagetta, Luigi A. Morrone, Maria Tiziana Corasaniti
Summary: Chronic pain is a common issue, especially in elderly individuals with cognitive impairment. This study highlights the potential of bergamot essential oil (BEO) in managing pain and agitation, providing a safe alternative to neuroleptics.
Article
Multidisciplinary Sciences
Stefan Baar, Masahiro Kuragano, Kiyotaka Tokuraku, Shinya Watanabe
Summary: This study aims to define a comprehensive approach to quantitatively estimate the physical cell activity based on migration and morphology using statistical analysis. The researchers present quantitative measurements of the influence of drugs on cell populations and have developed a customized deep learning cell detection and tracking procedure.
SCIENTIFIC REPORTS
(2022)
Article
Biology
Yuuki Hayakawa, Masak Takaine, Kien Xuan Ngo, Taiga Imai, Masafumi D. Yamada, Arash Badami Behjat, Kenichi Umeda, Keiko Hirose, Ayhan Yurtsever, Noriyuki Kodera, Kiyotaka Tokuraku, Osamu Numata, Takeshi Fukuma, Toshio Ando, Kentaro Nakano, Taro Q. P. Uyeda
Summary: Sub-stoichiometric binding of an actin-binding protein can induce structural changes in actin filaments and inhibit their movement, affecting actomyosin interactions and force generation.
LIFE SCIENCE ALLIANCE
(2022)
Review
Biochemistry & Molecular Biology
Maria Tiziana Corasaniti, Giacinto Bagetta, Luigi Antonio Morrone, Paolo Tonin, Kengo Hamamura, Takafumi Hayashi, Francesca Guida, Sabatino Maione, Damiana Scuteri
Summary: More than 80% of cancer patients experience cancer-related pain, which is difficult to manage, especially in the advanced stage. Recent evidence suggests that aromatherapy using essential oils can effectively reduce the intensity of cancer pain. This systematic review and meta-analysis evaluated the efficacy of aromatherapy in clinical studies on cancer pain and found significant benefits. However, more standardized and well-designed clinical trials are needed to establish a stronger evidence base for the use of essential oils in integrative oncology. PROSPERO registration: CRD42023393182.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Kohei Nishida, Kosuke Matsumura, Miki Tamura, Takuto Nakamichi, Keiya Shimamori, Masahiro Kuragano, Arif Md. Rashedul Kabir, Akira Kakugo, Susumu Kotani, Naoki Nishishita, Kiyotaka Tokuraku
Summary: The physical properties of cytoskeletal microtubules, regulated by microtubule-associated proteins (MAPs) such as MAP2, MAP4, and tau, have different effects on their cellular functions. Tau-bound microtubules exhibit a straighter morphology and lower flexibility compared to microtubules bound by MAP2 and MAP4 isoforms. In human neuroblastoma cells, the expression of full-length tau fused with EGFP leads to straighter microtubules in protrusions and fewer branches compared to cells expressing MAP2 and MAP4.
SCIENTIFIC REPORTS
(2023)
Article
Chemistry, Applied
Hisahiko Shibata, Mina Abe, Kazuya Sato, Koji Uwai, Kiyotaka Tokuraku, Toshifumi Iimori
Summary: Fluorescent carbon dots (CDs) emitting blue, orange, and green fluorescence were successfully synthesized via the microwave-assisted hydrothermal treatment of starch in an aqueous phosphoric acid solution. The CDs emitting blue fluorescence showed a high fluorescence quantum yield of 30%, comparable to that of semiconductor quantum dots. The formation of CDs and their aggregation process were monitored using spectroscopic approach, revealing the extraction of aggregations and the impact of aggregation on fluorescence quantum yield.
CARBOHYDRATE POLYMER TECHNOLOGIES AND APPLICATIONS
(2022)
Article
Chemistry, Medicinal
Shuang Mei, Su Jiang, Yuting Wang, Han Jing, Peng Yang, Miao-Miao Niu, Jindong Li, Kai Yuan, Yan Zhang
Summary: This study identifies a dual-targeting peptide, AP-1, that effectively inhibits variants of concern (VOCs) of SARS-CoV-2 without impairing host cell viability. The findings suggest that AP-1 could be a promising broad-spectrum agent for treating emerging VOCs of SARS-CoV-2.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Hyeonjun Lee, Ju Yeon Lee, Hyunsoo Jang, Hye Young Cho, Minhee Kang, Sang Hyun Bae, Suin Kim, Eunji Kim, Jaebong Jang, Jin Young Kim, Young Ho Jeon
Summary: By using liquid chromatography-tandem mass spectrometry and nuclear magnetic resonance experiments, we identified new chemical moieties that bind to the target sites of the protein of interest, allowing for reversible binding and protein degradation. This method has the potential to expand the application of PROTAC technology.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Yingying Li, Xiyou Du, Xinru Kong, Yuelin Fang, Zhijing He, Dongzhu Liu, Hang Wu, Jianbo Ji, Xiaoye Yang, Lei Ye, Guangxi Zhai
Summary: This study proposes a novel nanoplatform based on the autophagy cascade to overcome the obstacles in chemo-immunotherapy. The platform combines chemotherapy and starvation therapy to initiate pro-death autophagy and enhance antigen presentation, while also remodeling the immunosuppressive tumor microenvironment. Furthermore, the study discovers a new therapeutic direction for the respiration inhibitor 3-bromopyruvic acid (3BP) in cancer treatment. Overall, this study offers an opportunity to improve antitumor efficacy and boost immune responses.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Bingsi Wang, Mingxu Ma, Yusen Dai, Pengfei Yu, Liang Ye, Wenyan Wang, Chunjie Sha, Huijie Yang, Yingjie Yang, Yunjing Zhu, Lin Dong, Shujuan Wei, Linlin Wang, Jingwei Tian, Hongbo Wang
Summary: Breast cancer is a common malignant tumor in women, and drug resistance remains a clinical challenge. In this study, a novel compound, G-5b, was developed with potent antagonistic and degradation activities comparable to the current drug fulvestrant. G-5b also showed improved stability and solubility. Mechanistically, G-5b engages the proteasome pathway to degrade ER, inhibiting the ER signaling pathway and inducing apoptosis and cell cycle arrest. In animal models, G-5b exhibited superior pharmacokinetics and pharmacodynamics properties. Overall, G-5b is a promising long-acting SERD worthy of further investigation and optimization.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Karoline B. Waitman, Larissa C. de Almeida, Marina C. Primi, Jorge A. E. G. Carlos, Claudia Ruiz, Thales Kronenberger, Stefan Laufer, Marcia Ines Goettert, Antti Poso, Sandra V. Vassiliades, Vinicius A. M. de Souza, Monica F. Z. J. Toledo, Neuza M. A. Hassimotto, Michael D. Cameron, Thomas D. Bannister, Leticia Costa-Lotufo, Joa o A. Machado-Neto, Mauricio T. Tavares, Roberto Parise-Filho
Summary: A series of hybrid inhibitors combining pharmacophores of known kinase inhibitors and benzohydroxamate HDAC inhibitors were synthesized and evaluated for their anticancer activity and pharmacokinetic properties. Compounds 4d-f exhibited promising cytotoxicity against hematological cells and moderate activity against solid tumor models. Compound 4d showed potent inhibition of multiple kinase targets and had stable interactions with HDAC and members of the JAK family. These compounds showed selective cytotoxicity with minimal effects on non-tumorigenic cells and favorable pharmacokinetic profiles.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Michal Sulik, Diana Fontinha, Dietmar Steverding, Szymon Sobczak, Michal Antoszczak, Miguel Prudencio, Adam Huczynski
Summary: This study describes the synthesis of the first-in-class ivermectin derivatives obtained through derivatization of the C13 position, along with the unexpected rearrangement of the macrolide ring. These derivatives show potential for antiparasitic activity and are important for the development of new antiparasitic agents.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Jun Liu, Qiu-Xian Chen, Wen-Fu Wu, Dong Wang, Si -Yu Zhao, Jia-Hao Li, Yi-Qun Chang, Shao-Gao Zeng, Jia-Yi Hu, Yu-Jie Li, Jia-Xin Du, Shu-Meng Jiao, Hai-Chuan Xiao, Qiang Zhang, Jun Xu, Jian-Fu Zhao, Hai -Bo Zhou, Yong-Heng Wang, Jian Zou, Ping-Hua Sun
Summary: A new anti-infective drug strategy has been discovered to attenuate virulence and modulate inflammation caused by drug-resistant Pseudomonas aeruginosa infections. Compound 5f inhibits biofilm formation, macrophage migration, and inflammatory response induced by P. aeruginosa, showing potential as a novel candidate against drug-resistant infections.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Liuzeng Chen, Ke Wang, Lingyun Wang, Wei Wang, Lifan Wang, Jia Li, Xiaohan Liu, Mengya Wang, Banfeng Ruan
Summary: In this study, a series of novel anti-inflammatory compounds were designed and synthesized based on the natural product pterostilbene skeleton. Among them, compound 8 showed the highest activity and exhibited its effects through inhibition of pro-inflammatory cytokines by blocking the NF-KB/MAPK signaling pathway. Compound 8 also demonstrated a good relieving effect on acute colitis in mice and showed good safety in acute toxicity experiments.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Si-Min Liang, Gui-Bin Liang, Hui-Ling Wang, Hong Jiang, Xian-Li Ma, Jian-Hua Wei, Ri-Zhen Huang, Ye Zhang
Summary: A series of novel multi-target antitumor agents were designed, synthesized, and evaluated. Some compounds exhibited significant antitumor activity and one compound showed excellent efficacy, limited toxicity, and low resistance. Further mechanism studies revealed that the compound exerted antitumor effects through multiple pathways.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
