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
Neurosciences
Francois-Xavier Cantrelle, Anne Loyens, Xavier Trivelli, Oliver Reimann, Clement Despres, Neha S. Gandhi, Christian P. R. Hackenberger, Isabelle Landrieu, Caroline Smet-Nocca
Summary: Phosphorylation of Tau protein plays a critical role in the aggregation process observed in Alzheimer's disease brains. Recent research has highlighted the regulatory role of O-GlcNAcylation in modulating Tau phosphorylation and aggregation. Results showed that O-GlcNAcylation reduces phosphorylation of PHF-1 epitope, which is hyperphosphorylated in AD brains, and impacts the rate of fibrillar assembly in in-vitro assays.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Anna Pasieka, Dawid Panek, Natalia Szalaj, Alba Espargaro, Anna Wieckowska, Barbara Malawska, Raimon Sabate, Marek Bajda
Summary: The study identified a potent dual aggregation inhibitor for Alzheimer's disease, with compound 18 showing the most balanced and strong inhibitory effects on amyloid beta and tau aggregation. This compound also exhibited inhibitory activity against hBuChE, hBACE1, and A beta, and may provide insight into the design of future generations of aggregation inhibitors.
ACS CHEMICAL NEUROSCIENCE
(2021)
Article
Agriculture, Multidisciplinary
Roberto Tira, Giovanna Viola, Carlo Giorgio Barracchia, Francesca Parolini, Francesca Munari, Stefano Capaldi, Michael Assfalg, Mariapina D'Onofrio
Summary: Espresso coffee has a protective effect against neurodegenerative disorders such as Alzheimer's disease. The coffee extract contains caffeine and genistein, which prevent the aggregation and fibrillization of tau protein. Additionally, certain coffee compounds can bind to preformed tau fibrils.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Linlin Xu, Yuxun Ding, Feihe Ma, Yue Chen, Guidong Chen, Lin Zhu, Jiafu Long, Rujiang Ma, Yang Liu, Jianfeng Liu, Fan Huang, Linqi Shi
Summary: Researchers have developed a customized nanochaperone protein for targeting intracellular pathological tau in Alzheimer's disease. This protein effectively inhibits tau aggregation and improves cognitive deficits. The nanochaperone exhibits selectivity and does not interfere with normal tau function. This study provides valuable insights for the treatment of Alzheimer's disease and other neurodegenerative disorders.
Article
Chemistry, Multidisciplinary
Francesca Munari, Luca Mollica, Carlo Valente, Francesca Parolini, Elham Ataie Kachoie, Giorgio Arrigoni, Mariapina D'Onofrio, Stefano Capaldi, Michael Assfalg
Summary: The study reveals that E3 ligase CHIP can ubiquitinate Tau protein at multiple sites, even in the absence of molecular chaperones, providing mechanistic insight into the chaperone-independent engagement of a disordered protein by its E3 ligase.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Biochemistry & Molecular Biology
Ying-Ying Gao, Tao Zhong, Li-Qiang Wang, Na Zhang, Yan Zeng, Ji-Ying Hu, Hai-Bin Dang, Jie Chen, Yi Liang
Summary: Zinc promotes liquid-liquid phase separation and aggregation of full-length Tau, resulting in the formation of stress granules and interaction with G3BP1, leading to increased Tau filaments and neuronal toxicity. Additionally, zinc aggravates mitochondrial damage and reactive oxygen species production induced by Tau aggregation, further deteriorating the pathogenesis of Alzheimer's disease.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Article
Neurosciences
Yuxing Xia, Brach M. M. Bell, Justin D. D. Kim, Benoit I. I. Giasson
Summary: Tauopathies are neurodegenerative diseases characterized by the formation of tau brain aggregates. Imbalance of 3R and 4R tau isoforms is a contributing factor in the development of these diseases. The S356T tau mutation shows unique prion-like seeded aggregation, forming extensive Thioflavin positive aggregates. This finding will contribute to the understanding of diverse presentations of different tauopathies.
FRONTIERS IN NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Sehnaz Ferdosh, Senjuti Banerjee, Jayshree Singh, Chandana Barat
Summary: Alzheimer's disease is a neurodegenerative disease characterized by the aggregation of Tau protein and amyloid-beta peptides. Research has shown that the in vitro aggregation of A beta peptides in the vicinity of the ribosome can induce the co-aggregation of ribosomal components. The stoichiometry of RNA:protein and polyphenolic inhibitors also play a role in this process.
Article
Biochemistry & Molecular Biology
Huan-Huan Yin, Yin-Lei Han, Xiao Yan, Yi-Xin Guan
Summary: This study discovered that hematoxylin has dual functionality in inhibiting tau protein fibrillogenesis and remodeling pre-formed fibrils. It also reduces the accumulation of tau aggregates. Hematoxylin interacts with tau protein through various forces and reduces cytotoxicity. Therefore, it may be a promising candidate for the treatment of Alzheimer's disease.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Biochemistry & Molecular Biology
Vali Akbari, Soheila Mohammadi, Masomeh Mehrabi, Sirous Ghobadi, Alireza Farrokhi, Reza Khodarahmi
Summary: This study investigates the impact of cis-proline isomer on tau protein aggregation by replacing proline residues with alanine residues using genetic engineering. The results show that the trans isomer at the 232nd residue has reduced aggregation propensity. However, there is no significant difference between wild-type and mutant protein aggregations in terms of cell toxicity.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Article
Biochemistry & Molecular Biology
Ching-Hsuan Chou, Chia-Ron Yang
Summary: Evodiamine significantly reduces phosphorylated tau expression, reduces tau aggregation and neuronal cell death. Evodiamine exhibits neuroprotective effects by inhibiting glycogen synthase kinase 3 beta, cyclin-dependent kinase 5, and mitogen-activated protein kinase pathways.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Joao Filipe Neves, Olivia Petrvalska, Francesco Bosica, Francois-Xavier Cantrelle, Hamida Merzougui, Gavin O'Mahony, Xavier Hanoulle, Tomas Obsil, Isabelle Landrieu
Summary: Protein-protein interactions (PPIs) involving 14-3-3 proteins and Tau are potential targets for Alzheimer's disease treatment. Phosphorylation of Tau by PKA is crucial for the formation of a stable complex with 14-3-3 sigma, with an affinity in the 1-10 micromolar range. Each monomer of the 14-3-3 sigma dimer binds to two different phosphorylated peptides of Tau-PKA, suggesting a 2:1 stoichiometry for 14-3-3/Tau-PKA.
Article
Biochemistry & Molecular Biology
Shoaib Manzoor, Moustafa T. Gabr, Bisma Rasool, Kavita Pal, Nasimul Hoda
Summary: The study reported a new series of deoxyvasicinone analogues as dual inhibitors of acetylcholinesterase (AChE) and tau aggregation, demonstrating their potential as multitargeted ligands for Alzheimer's disease. Among the synthesized compounds, one particular compound showed significant inhibition of AChE activity and cellular tau oligomerization, highlighting its promising potential for anti-AD drug development.
BIOORGANIC CHEMISTRY
(2021)
Article
Chemistry, Physical
Wei Zhang, Nabin Kandel, Yiqun Zhou, Nathan Smith, Braulio C. L. B. Ferreira, Miranda Perez, Matteo L. Claure, Keenan J. Mintz, Chunyu Wang, Roger M. Leblanc
Summary: This study explored the efficacy of two types of carbon dots as nano-carriers for Alzheimer's disease therapy. The carbon dots successfully inhibited the aggregation of tau protein, demonstrating their potential for drug delivery in Alzheimer's treatment. These findings have significant implications for enhancing the delivery of drugs to target Alzheimer's pathology in the brain.
JOURNAL OF COLLOID AND INTERFACE SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Javier Oroz, Jin Hae Kim, Bliss J. Chang, Markus Zweckstetter
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2017)
Article
Multidisciplinary Sciences
Garima Jaipuria, Andrei Leonov, Karin Giller, Suresh Kumar Vasa, Lukasz Jaremko, Mariusz Jaremko, Rasmus Linser, Stefan Becker, Markus Zweckstetter
NATURE COMMUNICATIONS
(2017)
Article
Multidisciplinary Sciences
Susmitha Ambadipudi, Jacek Biernat, Dietmar Riedel, Eckhard Mandelkow, Markus Zweckstetter
NATURE COMMUNICATIONS
(2017)
Article
Biochemistry & Molecular Biology
Javier Oroz, Jin Hae Kim, Bliss J. Chang, Markus Zweckstetter
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2017)
Article
Biochemistry & Molecular Biology
Jeremy D. Baker, Lindsey B. Shelton, Dali Zheng, Filippo Favretto, Bryce A. Nordhues, April Darling, Leia E. Sullivan, Zheying Sun, Parth K. Solanki, Mackenzie D. Martin, Amirthaa Suntharalingam, Jonathan J. Sabbagh, Stefan Becker, Eckhard Mandelkow, Vladimir N. Uversky, Markus Zweckstetter, Chad A. Dickey, John Koren, Laura J. Blair
Article
Biochemistry & Molecular Biology
Rita Machado de Oliveira, Hugo Vicente Miranda, Laetitia Francelle, Raquel Pinho, Eva M. Szegoe, Renato Martinho, Francesca Munari, Diana F. Lazaro, Sebastien Moniot, Patricia Guerreiro, Luis Fonseca, Zrinka Marijanovic, Pedro Antas, Ellen Gerhardt, Francisco Javier Enguita, Bruno Fauvet, Deborah Penque, Teresa Faria Pais, Qiang Tong, Stefan Becker, Sebastian Kuegler, Hilal Ahmed Lashuel, Clemens Steegborn, Markus Zweckstetter, Tiago Fleming Outeiro
Article
Biochemistry & Molecular Biology
Elias Akoury, Guoli Ma, Segolene Demolin, Cornelia Broenner, Manuel Zocco, Alexandre Cirilo, Nives Ivic, Mario Halic
NUCLEIC ACIDS RESEARCH
(2019)
Review
Pharmacology & Pharmacy
Sally El Kantar, Bilal Nehmeh, Philippe Saad, Gabie Mitri, Celine Estephan, Mohamad Mroueh, Elias Akoury, Robin Taleb
DRUG DISCOVERY TODAY
(2020)
Article
Environmental Sciences
Josephine Al-Alam, Maurice Millet, Dani Khoury, Anais Rodrigues, Moustapha Harb, Elias Akoury, Sima Tokajian, Mahmoud Wazne
Summary: This study conducted a biomonitoring research of pesticides in an apple orchard using Cornu aspersum snails. The results showed higher pesticide levels in the center of the orchard, with semi-volatile pesticides being more likely to accumulate compared to non-volatile pesticides. The presence of semi-volatile pesticides in snails outside the orchard demonstrated their usefulness in monitoring off-site pesticide emissions.
Article
Chemistry, Multidisciplinary
Ali Yassin, Bilal Nehmeh, Sally El Kantar, Yara Al Kazzaz, Elias Akoury
Summary: Nuclear Magnetic Resonance (NMR) spectroscopy is essential for determining the structure and interactions of molecules. Residual Dipolar Coupling (RDC) provides global orientation information but requires the use of anisotropic orientation media. Anisotropic paramagnetic tags have been successful in biomolecular NMR, but their use in small organic molecules is still imperfect. This study proposes a strategy for synthesizing a lanthanide tag and measuring RDCs in target molecules.
Article
Multidisciplinary Sciences
Sally El Kantar, Ali Yassin, Bilal Nehmeh, Louis Labaki, Sara Mitri, Fatima Naser Aldine, Aaron Hirko, Sergio Caballero, Eileen Monck, Alejandra Garcia-Maruniak, Elias Akoury
Summary: Lemon balm, a herbal tea, has been used for soothing stomach cramps, indigestion, and nausea. One of its chemical constituents, rosmarinic acid (RA), has shown therapeutic potentials against cancer, inflammatory diseases, and neuronal diseases such as Alzheimer's disease (AD). This study successfully extracted and purified RA, determined its structure using nuclear magnetic resonance (NMR) spectroscopy, and investigated its anti-aggregation inhibition potentials, anti-cancer effects, and electrochemical properties. The data demonstrates that RA is a biologically active natural product with therapeutic potentials for drug discovery in AD, cancer therapy, and inflammatory diseases.
SCIENTIFIC REPORTS
(2022)
Article
Environmental Sciences
Josephine Al-Alam, Maurice Millet, Moustapha Harb, Elias Akoury, Sima Tokajian, Mahmoud Wazne
Summary: Juvenile Helix aspersa Muller were used to study the bioaccumulation of Cd, Cr, Cu, Fe, Mn, Ni, Pb, and Zn at agricultural and industrial sites in Lebanon. The results showed site-dependent metal bioaccumulation, with Fe and Cd being the most and least accumulated metals, respectively. The study also observed differences in bioaccumulation between soft tissue and shells. Time-dependent bioaccumulation results showed increased accumulation at agricultural sites and a slight decline at industrial sites. The findings suggest that H. aspersa is suitable for biomonitoring and assessing metal pollution and bioavailability.
ENVIRONMENTAL MONITORING AND ASSESSMENT
(2023)
Article
Chemistry, Applied
Elias Akoury, Najwa Mansour, Ghina Abdul Reda, Hani Dimassi, Layal Karam, Nisreen Alwan, Hussein F. Hassan
Summary: The aim of this study was to analyze toxic metals in rice from Lebanon and UAE, determine their contamination factors, and evaluate the potential health risks from rice consumption. The results indicate that a significant number of rice samples exceeded international limits for As, Cd, Hg, and Pb, with variations observed between Lebanon and UAE. Factors such as brand, country of origin, and collection time were found to play a significant role in rice contamination.
JOURNAL OF FOOD COMPOSITION AND ANALYSIS
(2023)
Article
Chemistry, Multidisciplinary
Bilal Nehmeh, Fatima Haydous, Elias Akoury
Summary: GC-EI-MS is commonly used for metabolite profiling, but it can't provide information on the molecular weight of unknown compounds. Chemical ionization (CI) technique combined with accurate mass measurement can be used to calculate the sum formulas of those compounds. Ultramark 1621 and PFK were found to be suitable mass calibrants for HRMS analysis, with PFK providing a fragmentation pattern similar to EI outcomes and Ultramark 1621 showing stable fragment intensities.
Article
Clinical Neurology
Hugo Vicente Miranda, Eva M. Szego, Luis M. A. Oliveira, Carlo Breda, Ekrem Darendelioglu, Rita M. de Oliveira, Diana G. Ferreira, Marcos A. Gomes, Ruth Rott, Marcia Oliveira, Francesca Munari, Francisco J. Enguita, Tania Simoes, Eva F. Rodrigues, Michael Heinrich, Ivo C. Martins, Irina Zamolo, Olaf Riess, Carlos Cordeiro, Ana Ponces-Freire, Hilal A. Lashuel, Nuno C. Santos, Luisa V. Lopes, Wei Xiang, Thomas M. Jovin, Deborah Penque, Simone Engelender, Markus Zweckstetter, Jochen Klucken, Flaviano Giorgini, Alexandre Quintas, Tiago F. Outeiro
