Article
Chemistry, Analytical
Zeeshan A. Khan, Seungkyung Park
Summary: In this study, a colorimetric assay based on the binding of Aβ(1-40) to gold nanoparticles and metal ions was proposed for the detection of Aβ. This newly developed assay showed good linearity and high sensitivity for the detection of Aβ(1-40) in biological or biomedical samples.
Article
Nutrition & Dietetics
Lifang Zhang, Jessica Cao, Haiqiang Yang, Phillip Pham, Umer Khan, Breanna Brown, Yanhong Wang, Tarek Zieneldien, Chuanhai Cao
Summary: Coffee consumption, regardless of brand or type, is beneficial for stalling the progression and development of A beta-related Alzheimer's disease (AD). All coffees tested have beneficial health effects for AD through lowering A beta 1-40 and A beta 1-42 production, with Dunkin' Donuts (R) medium roast coffee demonstrating the most consistent and optimal cell survival rates and A beta concentration, while Starbucks (R) coffee exhibited the highest cell toxicity rates among the tested coffees.
FRONTIERS IN NUTRITION
(2022)
Article
Biochemistry & Molecular Biology
Nikhil Agrawal, Adam A. Skelton, Emilio Parisini
Summary: Alzheimer's disease, characterized by the misfolding and aggregation of amyloid-beta (A beta) peptides, remains poorly understood in terms of its molecular mechanism of interaction with cell membranes. In this study, simulations were conducted to investigate the interaction between A beta 1-40 fibrils and different bilayers composed of DPPC and cholesterol. The results show the involvement of hydrophobic amino acid clusters, lysine residues, and C-terminal hydrophobic residues in the binding process. Furthermore, the data suggest that the binding affinity of A beta 1-40 fibrils to the membrane increases with the presence of cholesterol. These findings provide insights into potential target regions for the development of inhibitors against A beta oligomer/fibril-membrane interaction.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)
Article
Geriatrics & Gerontology
Meilin She, Suhang Shang, Ningwei Hu, Chen Chen, Liangjun Dang, Ling Gao, Shan Wei, Kang Huo, Jingyi Wang, Jin Wang, Qiumin Qu
Summary: The study found that elevated blood pressure levels were positively correlated with increased plasma A beta(1-40) levels in middle-aged and elderly ApoE epsilon 4 non-carriers.
FRONTIERS IN AGING NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Hanna Trebesova, Guendalina Olivero, Mario Marchi, Massimo Grilli
Summary: KLVFF is a small peptide with anti-Aβ aggregation properties that can potentially treat Alzheimer's disease by modulating cholinergic receptors. However, its activity on receptors requires external binding. Additionally, KLVFF does not affect specific cholinergic receptor subtypes and nicotinic receptors regulating noradrenaline release.
Article
Neurosciences
Qamar Zia, Md Tabish Rehman, Md Amiruddin Hashmi, Sahabjada Siddiqui, Abdulaziz Bin Dukhyil, Mohammad Z. Ahmed, Azfar Jamal, Saeed Banawas, Sami G. Almalki, Mohammad Owais, Hamad Qasem Aldhafeeri, Ibrahim M. Ibrahim, Wael Alturaiki, Mohamed F. AlAjmi, Mohammed Alsieni, Yaser E. Alqurashi
Summary: Alzheimer's disease is a common neurodegenerative disease, and flavonoids present in date palm could serve as antioxidants to combat memory loss and cognitive dysfunction. Diosmetin and Luteolin were found to be effective inhibitors of amyloid formation and exhibited high drug likeness scores. However, further experimental validation is required for these findings.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Paula Alexandra Postu, Marius Mihasan, Dragos Lucian Gorgan, Fatima Zahra Sadiki, Mostafa El Idrissi, Lucian Hritcu
Summary: The present study evaluated the potential medicinal effects of Pinus halepensis Mill. essential oil (PNO) in an Alzheimer's disease (AD) environment. The results showed that PNO has anxiolytic and antidepressant properties and can restore redox imbalance in rats with AD-like neuropsychiatric impairments. Additionally, PNO demonstrated beneficial effects against neuroinflammation and neuroapoptosis in the AD rat model induced by amyloid beta1-42 (A beta 1-42).
Article
Neurosciences
Nesa Ahmadi, Samaneh Safari, Naser Mirazi, Seyed Asaad Karimi, Alireza Komaki
Summary: Vanillic acid (VA) suppresses oxidative stress and reduces the effects of beta-amyloid (A beta) on learning and memory, making it a potential neuroprotective substance in Alzheimer's disease (AD).
BRAIN RESEARCH BULLETIN
(2021)
Article
Geriatrics & Gerontology
Te Wang, Wei Zhao, Yan Liu, Dandan Yang, Guohua He, Zhen Wang, Zsolt Radak
Summary: In this study, the down-regulation of inflammation-related miR-511-3p expression in AD patients and AD cell models was found. miR-511-3p expression was correlated with MMSE scores, MoCA scores, and inflammatory response in AD patients. miR-511-3p significantly reversed the effects of A beta (1-40) on inflammation in AD cells. miR-511-3p showed high diagnostic accuracy in distinguishing normal controls from AD patients.
EXPERIMENTAL GERONTOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Ali Abdulmawjood Mohammed, Sagar S. Barale, Subodh Ashok Kamble, Sneha B. Paymal, Kailas D. Sonawane
Summary: In this study, molecular docking and molecular dynamics simulations were used to explore the molecular mechanism of inhibition of early oligomerization and destabilization of preformed amyloid beta (Aβ) protofibrils by D-Trp-Aib. The results showed that D-Trp-Aib mainly binds to the aromatic and hydrophobic regions of Aβ monomers and protofibrils, inhibiting their aggregation and stabilization. The interaction between D-Trp-Aib and Aβ monomer stabilized the monomer and reduced the beta-sheet content, while the interaction with Aβ protofibril disrupted hydrophobic contacts and salt bridges, leading to its destabilization. Van der Waals and electrostatic interactions were found to be important in the binding of D-Trp-Aib to Aβ monomer and protofibril, respectively. These findings provide structural insights into the inhibition of Aβ oligomerization and destabilization of Aβ protofibril, which could be valuable for the development of novel inhibitors for Alzheimer's disease (AD).
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Clinical Neurology
Victoria Monge-Garcia, Lourdes Llorca-Tolon, Ruth Gasparini-Berenguer, Jose A. Monge-Argiles
Summary: This study aimed to evaluate the diagnostic gain of calculating the A beta(1-42)/A beta(1-40) ratio in identifying MCI patients with AD, compared to using only A beta(1-42). The results showed that using the A beta(1-42)/A beta(1-40) ratio significantly increased the accuracy of diagnosing amyloidosis in cerebrospinal fluid compared to using only A beta(1-42) levels.
REVISTA DE NEUROLOGIA
(2021)
Article
Biochemistry & Molecular Biology
Emma Shardlow, Bakhtbilland Khan, Christopher Exley
Summary: This study investigated the impact of different metal ions on the aggregatory behavior and size of A beta(1-42) under simulated physiological conditions. The results showed that Al3+ ions stabilized smaller, toxic intermediates while excess Cu2+ facilitated the formation of larger, more inert species. This suggests a complex relationship between metal ions and the toxicity of A beta(1-42).
JOURNAL OF TRACE ELEMENTS IN MEDICINE AND BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
William J. Howitz, Gretchen Guaglianone, Kate J. McKnelly, Katelyn Haduong, Shareen N. Ashby, Mohamed Laayouni, James S. Nowick
Summary: This study investigates the role of charge in the oligomeric assembly, toxicity, and membrane destabilization of peptides derived from A beta and its familial mutants. The findings suggest that the charge of the amino acid side chain, rather than its size or hydrophobicity, accounts for the differences in the behavior of the E22 familial mutants of A beta.
ACS CHEMICAL NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Ivan Sanchis, Roque Spinelli, Alvaro Siano
Summary: Alzheimer's disease is characterized by the presence of toxic beta-amyloid peptide aggregates. Recent discovery shows that Aβ(1-42) fibrils have catalytic activity on acetylcholine hydrolysis. This study examines the catalytic activity of Aβ(1-40) fibrils and finds that they display moderate enzymatic activity, suggesting a potential role of natural peptide aggregates as biocatalysts in neurological disorders.
Article
Medicine, Research & Experimental
Tahereh Alihosseini, Monireh Azizi, Nasser Abbasi, Shahram Mohammadpour, Maryam Bagheri
Summary: The study found that silibinin extract can improve behavioral performance in animals with Alzheimer's disease and reduce oxidative stress and expression of neurotrophic factors. Therefore, silibinin may act as a potential candidate for alleviating symptoms of Alzheimer's disease.
IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES
(2023)
Article
Microbiology
Corey Frazer, Mae Staples, Yoori Kim, Matthew Hirakawa, Maureen A. Dowell, Nicole Johnson, Aaron D. Hernday, Veronica H. Ryan, Nicolas L. Fawzi, Ilya J. Finkelstein, Richard J. Bennett
NATURE MICROBIOLOGY
(2020)
Article
Chemistry, Physical
Wai Shing Tang, Nicolas L. Fawzi, Jeetain Mittal
JOURNAL OF PHYSICAL CHEMISTRY B
(2020)
Article
Biochemistry & Molecular Biology
Veronica H. Ryan, Scott Watters, Joshua Amaya, Balabhadra Khatiwada, Vincenzo Venditti, Mandar T. Naik, Nicolas L. Fawzi
NUCLEIC ACIDS RESEARCH
(2020)
Article
Biochemistry & Molecular Biology
Theodora Myrto Perdikari, Anastasia C. Murthy, Veronica H. Ryan, Scott Watters, Mandar T. Naik, Nicolas L. Fawzi
Article
Biochemistry & Molecular Biology
Veronica H. Ryan, Theodora M. Perdikari, Mandar T. Naik, Camillo F. Saueressig, Jeremy Lins, Gregory L. Dignon, Jeetain Mittal, Anne C. Hart, Nicolas L. Fawzi
Summary: mRNA transport in neurons requires the formation of transport granules containing various protein components. Mutations in the hnRNPA2 protein can lead to increased aggregation and hereditary proteinopathy of neurons, myocytes, and bone. In vitro studies have shown that alterations in phosphorylation status of hnRNPA2 can affect its phase separation, partitioning specificity, assembly/disassembly, and link to neurodegenerative diseases.
Article
Chemistry, Physical
Wenwei Zheng, Gregory L. Dignon, Nina Jovic, Xichen Xu, Roshan M. Regy, Nicolas L. Fawzi, Young C. Kim, Robert B. Best, Jeetain Mittal
JOURNAL OF PHYSICAL CHEMISTRY B
(2020)
Article
Multidisciplinary Sciences
Feng Yuan, Haleh Alimohamadi, Brandon Bakka, Andrea N. Trementozzi, Kasey J. Day, Nicolas L. Fawzi, Padmini Rangamani, Jeanne C. Stachowiak
Summary: "Membrane bending is primarily driven by proteins with specific structural features, such as amphipathic helices and crescent-shaped scaffolds. Recent studies show that disordered protein domains can form liquid phases on membrane surfaces, creating compressive stress that leads to membrane curvature and the formation of protein-lined membrane tubules."
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Anna S. Bock, Anastasia C. Murthy, Wai Shing Tang, Nina Jovic, Frank Shewmaker, Jeetain Mittal, Nicolas L. Fawzi
Summary: Studies show that FUS is predominantly acetylated in human cell types and stress conditions, and N-terminal acetylation can reduce FUS LC aggregation without altering the structure.
Article
Cell Biology
Izzy Owen, Debra Yee, Hala Wyne, Theodora Myrto Perdikari, Victoria Johnson, Jeremy Smyth, Robert Kortum, Nicolas L. Fawzi, Frank Shewmaker
Summary: Myxoid liposarcoma is caused by a fusion protein of FUS and CHOP, leading to oncogenic transformation potentially through nuclear phase transitions. The formation of phase-separated condensates by FUS-CHOP, colocalizing with BRD4, may represent a novel oncogenic mechanism.
JOURNAL OF CELL SCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Nicolas L. Fawzi, Sapun H. Parekh, Jeetain Mittal
Summary: Biomolecular phase separation plays a crucial role in the formation of membraneless organelles and biomolecular condensates. Studying and controlling this process requires a multi scale view of biophysical properties, utilizing spectroscopic methods and computational simulations. Future developments should focus on visualizing the biophysical properties of condensates in cells.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Anastasia C. Murthy, Wai Shing Tang, Nina Jovic, Abigail M. Janke, Da Hee Seo, Theodora Myrto Perdikari, Jeetain Mittal, Nicolas L. Fawzi
Summary: FUS mediates phase separation in biomolecular condensates with the help of RGG domains and interacts with RNA polymerase II through various residue types and interaction modes. NMR visualization reveals a wider array of residue types and interaction modes stabilizing the phase-separated FUS and RNA polymerase II domains in transcriptional condensates.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Marissa G. Viola, Theodora Myrto Perdikari, Catherine E. Trebino, Negar Rahmani, Kaylee L. Mathews, Carolina Mejia Pena, Xien Yu Chua, Botai Xuan, Christopher J. LaBreck, Nicolas L. Fawzi, Jodi L. Camberg
Summary: This study demonstrates that the linker region of the essential bacterial division protein FtsZ is disordered in solution, and the amino acids in this region enhance degradation during polymerization-guided interactions.
Article
Biochemistry & Molecular Biology
Meenakshi Sundaram Kumar, Karly M. Stallworth, Anastasia C. Murthy, Su Min Lim, Nan Li, Aastha Jain, James B. Munro, Nicolas L. Fawzi, Clotilde Lagier-Tourenne, Daryl A. Bosco
Summary: Deficient nucleocytoplasmic transport is a pathogenic feature of ALS and FTD caused by FUS mutations. Wild-type and mutant FUS interact differently with Nup62, with mutant FUS showing cytoplasmic enrichment. Nup62's C-terminal domain plays a dominant role in inducing the formation of FUS/Nup62 amorphous assemblies.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Daria Maltseva, Sayantan Chatterjee, Chun-Chieh Yu, Mateusz Brzezinski, Yuki Nagata, Grazia Gonella, Anastasia C. Murthy, Jeanne C. Stachowiak, Nicolas L. Fawzi, Sapun H. Parekh, Mischa Bonn
Summary: Biomolecular condensates are dynamic membrane-less organelles that are rich in proteins and play important roles in various subcellular processes. However, abnormal phase transitions of disordered proteins in biomolecular condensates can lead to the formation of irreversible fibrils and aggregates, which are associated with neurodegenerative diseases. This study investigates the role of hydrophobic interactions in the phase transitions of the low-complexity domain of the FUS protein. The findings show that a hydrophobic interface drives fibril formation and molecular ordering of FUS at the air/water interface, resulting in solid-like film formation.
Review
Microbiology
Mae I. I. Staples, Corey Frazer, Nicolas L. L. Fawzi, Richard J. J. Bennett
Summary: Phase separation is a fundamental cellular process in which macromolecules partition into concentrated and immiscible phases. This process impacts diverse cellular processes in fungi, including autophagy regulation, cell signaling pathways, transcriptional circuits, and cell asymmetry establishment.
NATURE MICROBIOLOGY
(2023)