Article
Pharmacology & Pharmacy
Youn Young Lee, Jong In Han, Kyung Eun Lee, Sooyoung Cho, Eun Cheng Suh
Summary: Alzheimer's disease is a common neurodegenerative disease associated with pathological autophagy-lysosomal pathway dysfunction. Dexmedetomidine has been suggested as an adjuvant to general anesthesia, with advantages in reducing postoperative cognitive dysfunction. However, there is limited evidence on the effects of Dex on neuronal autophagy dysfunction in Alzheimer's disease models.
FRONTIERS IN PHARMACOLOGY
(2023)
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
Biochemistry & Molecular Biology
Veronica D'Ezio, Marco Colasanti, Tiziana Persichini
Summary: Amyloid-beta deposition in Alzheimer's disease induces oxidative stress and neuronal damage. Aβ(25-35) activates antioxidant response in astrocytes, leading to increased neuronal mortality due to glutamate release. Inhibition of System X-c(-) can reduce neuronal death and glutamate levels, with NMDA receptor activation playing a role in the pathway.
Review
Biochemistry & Molecular Biology
Chuli Song, Tianyu Zhang, Yingjiu Zhang
Summary: Soluble aggregation and deposition of A beta 42 are the initial pathological hallmarks of Alzheimer's disease. Anti-A beta 42 antibodies can inhibit the aggregation and toxicity of A beta 42, but their epitope specificity affects their binding affinity for different A beta 42 species.
Article
Biochemistry & Molecular Biology
Xueling Yuan, Zhuo Wang, Lei Zhang, Rubo Sui, Suliman Khan
Summary: Liquiritigenin was found to be an efficient inhibitor of tau amyloid fibril formation, reducing ROS and caspase-3 activity, and increasing CAT activity to alleviate neurotoxicity.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Medicine, Research & Experimental
Jeong-Hyun Yoon, Kumju Youn, Mira Jun
Summary: SHQA was found to have the strongest effect on Aβ-induced mitochondrial-associated oxidative stress and apoptosis, and exerted neuroprotective effects through activating the PI3K/Akt/Nrf2 pathway.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Biochemistry & Molecular Biology
Kazuma Murakami, Shiori Horii, Mizuho Hanaki, Kazuhiro Irie
Summary: The aggregation of Amyloid beta 42 in Alzheimer's disease involves nucleation and elongation phases. An orcein derivative, O4, has been shown to convert toxic oligomers into inert fibrils. Screening natural products for compounds that delay nucleation and promote elongation revealed several candidates that reduce the toxicity of Amyloid beta 42 against neuroblastoma cells. These compounds may interact with Amyloid beta 42 to shift its equilibrium from toxic oligomers to inert fibrils.
ACS CHEMICAL NEUROSCIENCE
(2021)
Article
Clinical Neurology
Rina Nakamura, Motomi Konishi, Youichirou Higashi, Motoaki Saito, Toshifumi Akizawa
Summary: In this study, two 5-mer synthetic peptides (GSGNR and GSGFK) were found to inhibit the aggregation of A beta 25-35 and resolve the already aggregated A beta 25-35. The peptide GSGFK was also effective in preventing short-term memory deficits induced by A beta 25-35 in mice and enhancing the phagocytic ability of microglia. These findings suggest that 5-mer peptides could be potential therapeutic drugs for Alzheimer's disease.
ALZHEIMERS RESEARCH & THERAPY
(2023)
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.
Article
Neurosciences
Meilin Wu, Clifford Z. Liu, Erika A. Barrall, Robert A. Rissman, William J. Joiner
Summary: The study demonstrates the role of Ly6h and NACHO in maintaining the balance of alpha 7 nicotinic acetylcholine receptors, which is disrupted in Alzheimer's disease leading to neurotoxic signaling.
JOURNAL OF NEUROSCIENCE
(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)
Article
Biochemistry & Molecular Biology
Rohmad Yudi Utomo, Yasunobu Asawa, Satoshi Okada, Hyun Seung Ban, Atsushi Yoshimori, Jorgen Bajorath, Hiroyuki Nakamura
Summary: A new compound B was found to have significantly higher inhibitory activity against Aβ aggregation compared to curcumin, while compound K showed low cytotoxicity on N2A cells and attenuated Aβ-induced cytotoxicity. These findings suggest potential for compound K in preventing neurotoxicity caused by Aβ aggregation.
BIOORGANIC & 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
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
Infectious Diseases
Ilaria Maria Saracino, Matteo Pavoni, Laura Saccomanno, Giulia Fiorini, Valeria Pesci, Claudio Foschi, Giulia Piccirilli, Giulia Bernardini, John Holton, Natale Figura, Tiziana Lazzarotto, Claudio Borghi, Berardino Vaira
Article
Biochemistry & Molecular Biology
Maria Lucia Schiavone, Alessandra Pecorelli, Brittany Woodby, Francesca Ferrara, Erika Pambianchi, Annalisa Santucci, Giuseppe Valacchi
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2020)
Editorial Material
Biochemistry & Molecular Biology
Raffaele Porta, Martino Bolognesi, Mauro Magnani, Francesca Cutruzzola, Eugenio Monti, Nazzareno Capitanio, Daniele Condorelli, Fulvio Della Ragione, Luca Federici, Gianfranco Gilardi, Silvana Hrelia, Antonio Lucacchini, Annalisa Santucci, Claudia Martini, Rosario Ammendola, Vittorio Bellotti, Saverio Bettuzzi, Donatella Caruso, Mauro Maccarrone, Alberto Passi, Luigi Palmieri, Margherita Ruoppolo
Letter
Medicine, General & Internal
Antonio Ponzetto, Natale Figura, Giulia Bernardini
INTERNAL AND EMERGENCY MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Stefano Barbera, Luisa Raucci, Roberta Lugano, Gian Marco Tosi, Anna Dimberg, Annalisa Santucci, Federico Galvagni, Maurizio Orlandini
Summary: The study reveals a signaling pathway triggered by CD93 that regulates actin cytoskeletal dynamics responsible for endothelial cell adhesion.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Silvia Galderisi, Martina Rossi, Vittoria Cicaloni, Ranieri Rossi, Daniela Giustarini, Ottavia Spiga, Laura Tinti, Laura Salvini, Cristina Tinti, Daniela Braconi, Lia Millucci, Pietro Lupetti, Filippo Prischi, Giulia Bernardini, Annalisa Santucci
Summary: This study evaluated the effect of homogentisic acid (HGA) on autophagy in a human chondrocytic cell line as an alkaptonuria (AKU) model. The results showed that HGA increased autophagy as a protective mechanism, but in a chronic state, HGA-induced oxidative stress decreased autophagy and activated chondrocyte apoptosis. These findings provide new perspectives for understanding the mechanism of AKU.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2022)
Review
Agriculture, Multidisciplinary
Paolo Governa, Giulia Bernardini, Daniela Braconi, Fabrizio Manetti, Annalisa Santucci, Elena Petricci
Summary: The serendipitous discovery of HPPD inhibitors from allelopathic plants has paved the way for the search of new and effective herbicidal agents. Various active and selective compounds have been found, including cyclohexane-based triketones, pyrazole-based diketones, and diketonitriles. Efforts have also been made to enhance inhibitory constant and herbicidal activity, as well as to broaden weed control and ensure crop safety. HPPD inhibitors have also shown potential as therapeutic agents and insecticides. Structure-activity relationship analysis can provide suggestions for the development of next generation optimized compounds.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2022)
Article
Biology
Alfonso Trezza, Claudia Mugnaini, Federico Corelli, Annalisa Santucci, Ottavia Spiga
Summary: This study proposes a computational strategy for identifying novel multi-target scaffolds against SARS-CoV-2 using bioinformatics methods. The study provides insights into the potential mechanisms of action and suggests new approaches for the rapid identification of multi-target inhibitors.
Review
Chemistry, Medicinal
Luisa Frusciante, Anna Visibelli, Michela Geminiani, Annalisa Santucci, Ottavia Spiga
Summary: Computational tools play a central role in drug discovery and development by analyzing large amounts of data. The availability of high throughput and affordable omics technologies has exponentially increased scientific data volume. The quality of data and speed of in silico predictions being validated in vitro are crucial for accelerating clinical laboratory medicine and Precision Medicine. Personalized medicine relies on gathering as much information and data as possible to understand individual drug responses and identify biomarkers accurately describing the risk signals for specific diseases. Biomarkers also play an increasing role in early drug discovery to reduce development time. This review article discusses the application of Artificial Intelligence in the drug discovery pipeline and its potential for Translational Precision Medicine.
CURRENT TOPICS IN MEDICINAL CHEMISTRY
(2022)
Article
Genetics & Heredity
Paolo Poli, Luana Peruzzi, Pierdomenico Maurizi, Antonella Mencucci, Antonella Scocca, Simona Carnevale, Ottavia Spiga, Annalisa Santucci
Summary: This study provides evidence that certain polymorphic candidate genes may be associated with the effects of cannabis, including pain management and side effects. Genetic makeup can be a predictive factor in the response to cannabis therapy.
Article
Biochemistry & Molecular Biology
Daniela Grasso, Michela Geminiani, Silvia Galderisi, Gabriella Iacomelli, Luana Peruzzi, Barbara Marzocchi, Annalisa Santucci, Andrea Bernini
Summary: Alkaptonuria is a metabolic disease caused by the accumulation of homogentisic acid, leading to connective tissue pigmentation and the development of osteoarthritis. The molecular mechanisms underlying the severity of the disease are not fully understood, but metabolomics studies have provided insights into the pathways involved and potential biomarkers that can aid in future treatment development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Daniela Braconi, Michela Geminiani, Eftychia Eirini Psarelli, Daniela Giustarini, Barbara Marzocchi, Ranieri Rossi, Giulia Bernardini, Ottavia Spiga, James A. Gallagher, Kim-Hanh Le Quan Sang, Jean-Baptiste Arnoux, Richard Imrich, Mohammed S. Al-Sbou, Matthew Gornall, Richard Jackson, Lakshminarayan R. Ranganath, Annalisa Santucci
Summary: Nitisinone (NTBC) has limited effects on oxidative stress and inflammation in patients with alkaptonuria (AKU), as observed by levels of Serum Amyloid A (SAA) and other markers.
Review
Biochemistry & Molecular Biology
Daniela Grasso, Silvia Galderisi, Annalisa Santucci, Andrea Bernini
Summary: When a protein fails to fold correctly, it can lead to diseases. These protein conformational disorders occur due to gene mutations that cause abnormal folding and can result in loss of function or improper localization. Pharmacological chaperones are small molecules that help restore proper folding, and computational structural biology tools are used to study these proteins and develop rational drug design.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Anna Visibelli, Bianca Roncaglia, Ottavia Spiga, Annalisa Santucci
Summary: Emerging machine learning technologies have great potential in improving the research and treatment of rare diseases by quickly identifying patterns and associations, predicting disease progression, and discovering targeted treatments. This review focuses on rare diseases with a prevalence rate not exceeding 1-9/100,000 on Orphanet and provides effective methods and guidance for clinicians and researchers in the application of AI in this field.
Article
Biochemistry & Molecular Biology
Anna Visibelli, Luana Peruzzi, Paolo Poli, Antonella Scocca, Simona Carnevale, Ottavia Spiga, Annalisa Santucci
Summary: Conventional therapy options for chronic pain are insufficient, leading patients to seek alternative medical treatments like medical cannabis. However, there is limited knowledge about the efficacy, dosage, administration methods, and side effects of commonly used cannabis products. Pharmacogenetics could provide a solution by identifying polymorphic genes that influence the pharmacodynamics and pharmacokinetics of cannabis. By collecting and analyzing data from patients treated with cannabis and genotyped for candidate polymorphic genes, machine learning can demonstrate the relationship between gene polymorphisms and pain reduction, improving therapeutic outcomes and minimizing side effects.
