Article
Biochemistry & Molecular Biology
Sheng Zhang, Gretchen Guaglianone, Michael A. Morris, Stan Yoo, William J. Howitz, Li Xing, Jian-Guo Zheng, Hannah Jusuf, Grace Huizar, Jonathan Lin, Adam G. Kreutzer, James S. Nowick
Summary: Fluorescent derivatives of beta-amyloid peptides are useful for studying interactions with cells. This study presents a method for expressing N-terminal cysteine Aβ peptides and conjugating them with fluorophores or biotin, yielding labeled Aβ peptides that behave similarly to unlabeled ones. The labeled Aβ peptides were successfully used in interactions with mammalian cells and bacteria, demonstrating their potential as valuable tools for researchers.
Article
Engineering, Biomedical
Huan He, Juan Xu, Chen-Qiao Li, Tian Gao, Peng Jiang, Feng-Lei Jiang, Yi Liu
Summary: By combining in vitro experiments and simulations, it was found that the thermodynamics and kinetics of fibril elongation on different oxidative degrees of graphene oxide (GO) surfaces vary. Low oxidative GO-10 promotes fibril elongation, while both high oxidative GO-20 and GO-40 inhibit it. The computational results indicate that GOs regulate filament growth by balancing the promoting and retarding effects of monomer templating and capturing during docking and locking phases.
ADVANCED HEALTHCARE MATERIALS
(2021)
Article
Biochemistry & Molecular Biology
Lei Gu, Zhefeng Guo
Summary: The formation of A beta oligomers and fibrils is crucial in Alzheimer's disease pathogenesis. A beta 42 and A beta 40 interact with each other influencing their aggregation, and A beta 40 has been shown to reduce plaque pathology in mouse models. The study suggests that A beta 42 and A beta 40 can form mixed oligomers with direct molecular interactions.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Allison Yoon, James Zhen, Zhefeng Guo
Summary: β amyloid 42 plays a central role in the pathogenesis of Alzheimer's disease, forming toxic oligomers in addition to insoluble fibrils. Our study on the structural dynamics of β amyloid 42 globulomers revealed residues 31-34 as the most stable segment, suggesting a lack of well-packed structural core in the globulomers.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Chemistry, Multidisciplinary
Chendi Zhan, Zenghui Lao, Yiming Tang, Qin Qiao, Guanghong Wei
Summary: The simulations showed that two enantiomeric catechins had a stronger disruptive effect on Aβ(42) protofibril compared to their stereo isomer epicatechin. The different protofibril-disruptive effects were mainly attributed to the steric effect caused by conformational differences.
CHEMICAL COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Li Wang, Kilho Eom, Taeyun Kwon
Summary: The study found that in the initial stage of aggregation process for both Aβ40 and Aβ42, multiple particles are formed which later self-assemble to form amyloid fibrils of different shapes. Different aggregation pathways of Aβ isoforms lead to amyloid fibrils with contrasting structures.
Article
Neurosciences
Antonio J. Figueira, Joana Saavedra, Isabel Cardoso, Claudio M. Gomes
Summary: Extracellular aggregation of the amyloid-beta 1-42 peptide is a major characteristic of Alzheimer's disease (AD), and recent studies have shown that the intermediate oligomers of amyloid-beta are more cytotoxic than mature fibrils. In this study, the researchers investigated how different chaperone multimers of S100B, a signaling protein increased in AD, influence the formation of amyloid-beta oligomers. It was found that dimeric S100B-Ca2+ C drastically decreased the rate of oligomerization and levels of amyloid-beta oligomers, while tetrameric apo-S100B inhibited both oligomerization and fibril elongation. These findings highlight the potential neuroprotective role of different S100B multimers in AD.
FRONTIERS IN NEUROSCIENCE
(2023)
Editorial Material
Biochemistry & Molecular Biology
Hubert Santuz, Phuong H. Nguyen, Fabio Sterpone, Philippe Derreumaux
Summary: This study explores the early aggregation steps of A beta 42 using the deep learning method AlphaFold2 and provides insights into the structure determination of A beta 42 monomers up to hexamers.
ACS CHEMICAL NEUROSCIENCE
(2022)
Article
Chemistry, Medicinal
Son Tung Ngo, Trung Hai Nguyen, Van V. Vu
Summary: The folding/misfolding of membrane-permiable Amyloidbeta (Aβ) peptides is likely associated with the advancing stage of Alzheimer's disease (AD) by disrupting Ca2+ homeostasis. The secondary structure of transmembrane Aβ peptides tends to have different propensities compared to those in solution and forms a pore structure. Although the formation of the β-barrel structure was not observed during the simulation, it is likely to form when the simulation time is further extended.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Biochemistry & Molecular Biology
Phuong H. Nguyen, Philippe Derreumaux
Summary: This study used molecular dynamics simulations to reveal the interaction between A beta 42 oligomers and lipid bilayer membranes. The results showed significant structural rearrangements, resulting in the formation of two trimers and one hexamer, accompanied by membrane disruption and water permeation.
ACS CHEMICAL NEUROSCIENCE
(2023)
Article
Chemistry, Multidisciplinary
Zhengxin Yu, Weijie Guo, Shrey Patel, Hong-Jun Cho, Liang Sun, Liviu M. Mirica
Summary: This study developed twelve small molecule compounds with different amphiphilic properties, which showed high binding affinity to the hallmark Aβ plaques and oligomers of Alzheimer's disease. These compounds also exhibited the ability to alleviate Cu2+-Aβ induced toxicity and disrupt the interactions between Aβ oligomers and cell membranes.
Article
Biochemistry & Molecular Biology
Sarah R. Ball, Julius S. P. Adamson, Michael A. Sullivan, Manuela R. Zimmermann, Victor Lo, Maximo Sanz-Hernandez, Xiaofan Jiang, Ann H. Kwan, Andre D. J. McKenzie, Eryn L. Werry, Tuomas P. J. Knowles, Michael Kassiou, Georg Meisl, Matthew H. Todd, Peter J. Rutledge, Margaret Sunde
Summary: Alzheimer's disease poses a growing burden on society and the economy, making effective therapies urgently needed. Researchers have developed small molecules that can limit the conversion of amyloid monomers into toxic oligomers and fibrils, potentially offering a way to modulate the disease outcome. By sequestering the amyloid monomers, these compounds prevent the formation of cytotoxic aggregates and disrupt the autocatalytic process that generates toxic oligomers. The modular design of these inhibitors allows for future exploration and investigation of the different species involved in amyloid assembly.
ACS CHEMICAL NEUROSCIENCE
(2022)
Article
Chemistry, Physical
Fangying Li, Chendi Zhan, Xuewei Dong, Guanghong Wei
Summary: Resveratrol (RSV) and epigallocatechin-3-gallate (EGCG) have been found to inhibit the aggregation of amyloid-beta protein (A beta) and may be promising strategies for treating Alzheimer's disease (AD). However, the specific mechanisms of how RSV inhibits A beta(42) aggregation and disrupts A beta(42) protofibril, as well as the differences between RSV and EGCG in their inhibitory/disruptive effects, still need further investigation.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2021)
Article
Chemistry, Physical
Brian Andrews, Thomas Ruggiero, Brigita Urbanc
Summary: It is known that self-assembly of amyloid beta-protein (A beta) is related to the development of Alzheimer's disease. However, the physiological function of A beta interacting with lipids is still not fully understood. This study investigates the conformational dynamics of A beta 42 monomer in water with different concentrations of salt and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) lipids. The results show that salt promotes long-range interactions in A beta 42, resulting in more compact conformations. On the other hand, lipids induce unfolding of A beta 42 and enhance the stability of certain regions. At high lipid concentration, salt enables interaction between the N-terminal region of A beta 42 and lipids, leading to the formation of a parallel beta-strand. A beta 42 forms stable complexes with lipids, where the protein adheres to the lipid cluster rather than being embedded in it. The inability of A beta 42 monomer to embed into the lipid cluster may play a role in maintaining the integrity of the blood-brain barrier and preventing damage to cellular membranes.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2023)
Article
Multidisciplinary Sciences
Mantas Ziaunys, Andrius Sakalauskas, Kamile Mikalauskaite, Vytautas Smirnovas
Summary: Protein aggregation in the form of amyloid fibrils is associated with the development of various neurodegenerative disorders. Despite extensive research, the process of aggregate formation is not fully understood. It has been observed that α-synuclein and amyloid beta aggregates can undergo structural rearrangements after long-term incubation. This study investigates the impact of elevated temperature on the restructuring of four different conformation α-synuclein amyloid fibrils, and demonstrates that this structural alteration occurs within a relatively short period of time.
Review
Plant Sciences
Amit Kumar, Marika Premoli, Francesca Aria, Sara Anna Bonini, Giuseppina Maccarinelli, Alessandra Gianoncelli, Maurizio Memo, Andrea Mastinu
Review
Biochemistry & Molecular Biology
Andrea Mastinu, Amit Kumar, Giuseppina Maccarinelli, Sara Anna Bonini, Marika Premoli, Francesca Aria, Alessandra Gianoncelli, Maurizio Memo
Article
Clinical Neurology
Lindsey Isla Sinclair, Amit Kumar, Taher Darreh-Shori, Seth Love
ALZHEIMERS RESEARCH & THERAPY
(2019)
Article
Clinical Neurology
Rajnish Kumar, Amit Kumar, Agneta Nordberg, Bengt Langstrom, Taher Darreh-Shori
ALZHEIMERS & DEMENTIA
(2020)
Review
Plant Sciences
A. Kumar, M. Memo, A. Mastinu
Article
Chemistry, Multidisciplinary
Ananya Sengupta, Josue Liriano, Ewa A. Bienkiewicz, Brian G. Miller, James H. Frederich
Article
Pharmacology & Pharmacy
Amit Kumar, Rajnish Kumar, John Flanagan, Bengt Langstrom, Lars Bjorndahl, Taher Darreh-Shori
BIOCHEMICAL PHARMACOLOGY
(2020)
Article
Biochemistry & Molecular Biology
Amit Kumar, Niina A. Koistinen, Mona-Lisa Malarte, Inger Nennesmo, Martin Ingelsson, Bernardino Ghetti, Laetitia Lemoine, Agneta Nordberg
Summary: The study demonstrates that the novel astrocytic PET ligand BU99008 can visualize reactive astrogliosis in postmortem AD brains and proposes a multiple binding site model for different ligands in AD and control brains. The data shows significant differences in the proportion and affinities of binding sites between AD and control groups, indicating potential targets for future research.
MOLECULAR PSYCHIATRY
(2021)
Review
Biochemistry & Molecular Biology
Amit Kumar, Igor C. Fontana, Agneta Nordberg
Summary: Astrocytes play a crucial role in brain functioning and are involved in the pathophysiology of Alzheimer's disease and other neurodegenerative disorders through reactive astrogliosis.
JOURNAL OF NEUROCHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Anurag T. K. Baidya, Amit Kumar, Rajnish Kumar, Taher Darreh-Shori
Summary: This study investigates the interaction between amyloid-beta (A beta) peptides and choline acetyltransferase (ChAT), an important enzyme in acetylcholine homeostasis. Through molecular docking and dynamics analysis, the stability and interaction mechanism of the ChAT-A beta complex were explored. The results supported the hypothesis that A beta peptides, particularly A beta(42), act as endogenous ChAT-Potentiating-Ligand (CPL) and play a role in regulating acetylcholine homeostasis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Clinical Neurology
Yang Yang, Wenjuan Zhang, Alexey G. Murzin, Manuel Schweighauser, Melissa Huang, Sofia Lovestam, Sew Y. Peak-Chew, Takashi Saito, Takaomi C. Saido, Jennifer Macdonald, Isabelle Lavenir, Bernardino Ghetti, Caroline Graff, Amit Kumar, Agneta Nordberg, Michel Goedert, Sjors H. W. Scheres
Summary: The high-resolution cryo-EM structures of A beta filaments with the Arctic mutation were reported in this study. Most of the filaments consist of two pairs of non-identical protofilaments, sharing a common substructure with the folds of type I and type II A beta 42. There are subtle conformational changes in the human Arctic folds, which may be due to the lack of a side chain at G22.
ACTA NEUROPATHOLOGICA
(2023)
Article
Biochemistry & Molecular Biology
Mona-Lisa Malarte, Per-Goran Gillberg, Amit Kumar, Nenad Bogdanovic, Laetitia Lemoine, Agneta Nordberg
Summary: Recent studies have revealed the complexity and heterogeneity of tau pathology in Alzheimer's disease (AD) and primary tauopathies, challenging the classical classification approach. New second-generation tau PET tracers can help differentiate AD from non-AD tauopathies and show different binding properties.
MOLECULAR PSYCHIATRY
(2023)
Correction
Biochemistry & Molecular Biology
Mona-Lisa Malarte, Per-Goran Gillberg, Amit Kumar, Nenad Bogdanovic, Laetitia Lemoine, Agneta Nordberg
MOLECULAR PSYCHIATRY
(2023)
Review
Clinical Neurology
Igor C. Fontana, Amit Kumar, Agneta Nordberg
Summary: This review discusses the connection between the cholinergic and amyloid cascade hypotheses of Alzheimer's disease (AD) pathogenesis, focusing on the expression of alpha 7 nicotinic acetylcholine receptors (alpha 7nAChRs) by astrocytes and its correlation with amyloid-beta pathology. The search for biomarkers beyond amyloid-beta and tau in AD research has led to a recognition of the importance of astrocytes, which play a crucial role in metabolic homeostasis and respond rapidly to brain pathology in the early stages of AD. Upregulation of astrocytic alpha 7nAChRs is associated with A beta pathology in AD brains, making it a potential biomarker and target for therapeutic interventions.
NATURE REVIEWS NEUROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Junhao Li, Amit Kumar, Bengt Langstrom, Agneta Nordberg, Hans Agren
Summary: In this study, the binding mechanisms of 10 PET tracers for PSP tau, CBD, and AD tau pathologies were investigated. The structure-activity relationships, binding preferences, intermolecular interactions, role of polar/charged residues, induced-fit mechanisms, grove closures, and folding patterns for these tracers in different tau fibrils were evaluated. The findings fill in the knowledge gap regarding the potential binding mechanisms of these tracers and are important for the design of highly selective novel PET tracers for tauopathies.
ACS CHEMICAL NEUROSCIENCE
(2023)