Article
Immunology
Megan J. J. Lantz, Alyssa M. M. Roberts, Donovan D. D. Delgado, Robert A. A. Nichols
Summary: Alzheimer's disease is characterized by the accumulation of amyloid beta (Aβ) and neurofibrillary tangles, leading to chronic neuroinflammation. The N-terminal Aβ fragment and N-Aβ core have been shown to protect against neurodegeneration. This study provides evidence that these fragments can also alleviate persistent neuroinflammation in Alzheimer's disease.
JOURNAL OF NEUROINFLAMMATION
(2023)
Article
Biochemistry & Molecular Biology
Fufeng Liu, Wenjuan Wang, Zhenquan Xuan, Luying Jiang, Beibei Chen, Qinchen Dong, Fang Zhao, Wei Cui, Li Li, Fuping Lu
Summary: This study found that Fast Green FCF (FGF) can effectively inhibit Aβ-induced neurotoxicity by reducing Aβ fibrillogenesis, disintegrating mature fibrils, decreasing Aβ-induced cytotoxicity, and improving Aβ-induced learning and memory impairments. Molecular dynamics simulations demonstrated that FGF can interact with Aβ through various mechanisms to reduce its neurotoxic effects.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Biochemistry & Molecular Biology
Yu Zhang, Yuying Liu, Wenhui Zhao, Yunxiang Sun
Summary: The study demonstrates that SWCNT-OH has excellent anti-amyloid properties, inhibiting the fibrillization of beta 2m(21)(-)(31) peptides and destroying pre-formed proto-fibrils.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Biochemistry & Molecular Biology
Oliver D. Kennedy-Britten, Nadiyah Al-Shammari, James A. Platts
Summary: Our study utilized MD simulations to investigate the impact of N-terminus mutants of copper-bound Aβ peptide on secondary structure, stability, and conformational changes. Results show marked and varied effects of mutations compared to the wild-type peptide, with differences in stability and conformation observed.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2021)
Article
Biochemistry & Molecular Biology
Vahid Zarezade, Zahra Nazeri, Shirin Azizidoost, Maryam Cheraghzadeh, Hossein Babaahmadi-Rezaei, Alireza Kheirollah
Summary: In this study, the effects of A beta on ABCA1 protein levels were investigated in microglia, astrocytes, and neurons using in vitro and in silico experiments. It was found that A beta significantly increased the protein levels of ABCA1 in these cells, but decreased its ability to efflux cholesterol. Molecular docking and molecular dynamics simulation revealed that A beta inhibited the function of ABCA1 by obstructing the extracellular tunnel.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Multidisciplinary Sciences
Hebah Fatafta, Mohammed Khaled, Michael C. Owen, Abdallah Sayyed-Ahmad, Birgit Strodel
Summary: Evidence suggests that the neuronal cell membrane is the main site of oligomer-mediated neuronal toxicity in Alzheimer's disease caused by amyloid-beta peptides. Interactions between amyloid-beta oligomers and the neuronal membrane decrease the propensity of beta-sheet formation in the oligomers. Gangliosides GM1 are identified as the main lipid interaction partners of A beta 42.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Chemistry, Multidisciplinary
Yunxiang Sun, Aleksandr Kakinen, Xulin Wan, Niamh Moriarty, Cameron P. J. Hunt, Yuhuan Li, Nicholas Andrikopoulos, Aparna Nandakumar, Thomas P. Davis, Clare L. Parish, Yang Song, Pu Chun Ke, Feng Ding
Summary: This study provides evidence of the structure, dynamics and toxicity of A beta 42 oligomers through synergistic in silico, in vitro and in vivo validations, highlighting their role as toxic intermediates in the early aggregation of amyloid peptides.
Article
Biology
Nadine T. T. Werner, Philipp Hoegel, Gokhan Guener, Walter Stelzer, Manfred Wozny, Marlene Assfalg, Stefan F. Lichtenthaler, Harald Steiner, Dieter Langosch
Summary: Intramembrane proteases are crucial in biology and medicine, but how they determine the cleavability of a substrate transmembrane (TM) domain remains unclear. This study shows that the conformational flexibility of the TM domain plays a role in substrate cleavability by gamma-secretase. Specifically, the N-terminal half of the TM helix and the C-terminal TM sequence are important for robust cleavability. The results further enhance our understanding of the mechanisms underlying intramembrane proteolysis.
COMMUNICATIONS BIOLOGY
(2023)
Article
Engineering, Multidisciplinary
Bushu Peng, Shaoying Xu, Yue Liang, Xiaoyan Dong, Yan Sun
Summary: This study investigates the impact of phenol-soluble modulin (PSM) alpha 3, a protein secreted by Staphylococcus aureus, on the aggregation of amyloid beta-protein (A beta) related to Alzheimer's disease (AD). The results show that PSM alpha 3 monomer inhibits A beta aggregation and changes the aggregation pathway, while PSM alpha 3 oligomers promote A beta aggregation. Molecular dynamics simulations reveal the molecular interactions between A beta and PSM alpha 3 of different structures.
Article
Clinical Neurology
Loan Vaillant-Beuchot, Arnaud Mary, Raphaelle Pardossi-Piquard, Alexandre Bourgeois, Inger Lauritzen, Fanny Eysert, Paula Fernanda Kinoshita, Julie Cazareth, Celine Badot, Konstantina Fragaki, Renaud Bussiere, Cecile Martin, Rosanna Mary, Charlotte Bauer, Sophie Pagnotta, Veronique Paquis-Flucklinger, Valerie Buee-Scherrer, Luc Buee, Sandra Lacas-Gervais, Frederic Checler, Mounia Chami
Summary: Recent evidence suggests that APP-CTFs may trigger AD pathology, while mitochondrial dysfunction is considered an early event in AD development. Accumulation of APP-CTFs can lead to mitochondrial morphological changes and impaired basal mitophagy, possibly playing a crucial role in AD pathogenesis.
ACTA NEUROPATHOLOGICA
(2021)
Article
Neurosciences
Valentina Latina, Giacomo Giacovazzo, Federica Cordella, Bijorn Omar Balzamino, Alessandra Micera, Monica Varano, Cristina Marchetti, Francesca Malerba, Rita Florio, Bruno Bruni Ercole, Federico La Regina, Anna Atlante, Roberto Coccurello, Silvia Di Angelantonio, Pietro Calissano, Giuseppina Amadoro
Summary: The retina and optic nerve are sites of extra-cerebral manifestations of Alzheimer's Disease, with tau protein truncation leading to pathological changes and administration of the specific 12A12mAb showing beneficial effects on ocular injury. This research opens new avenues for the clinical management of cerebral and extracerebral AD signs by targeting tau protein modifications and their neuroprotective actions.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2021)
Article
Clinical Neurology
Lei Liu, Hyunchang Kwak, Trebor L. Lawton, Shan-Xue Jin, Angela L. Meunier, Yifan Dang, Beth Ostaszewski, Alison C. Pietras, Andrew M. Stern, Dennis J. Selkoe
Summary: The study developed a new method for detecting and quantifying soluble oligomers of amyloid beta protein in human plasma. The method is highly sensitive, cost-effective, and suitable for high throughput analysis.
ALZHEIMERS & DEMENTIA
(2022)
Article
Biochemistry & Molecular Biology
Siddhartha Banerjee, Mohtadin Hashemi, Karen Zagorski, Yuri L. Lyubchenko
Summary: The presence of cholesterol in lipid bilayers significantly enhances the aggregation process of Aβ42 at low concentrations, indicating that the lipid composition plays a crucial role in controlling the self-assembly of Aβ oligomers in cellular membranes.
ACS CHEMICAL NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Jean-Numa Gillet
Summary: The study unravels the binding mechanisms of APOE4 associated with Alzheimer's disease, showing that when bound to the amyloid-beta peptide, APOE4 undergoes misfolding and increased deposition, potentially leading to the disease. Immunotherapies targeting APOE4 are promising for drug design, but the focus should be on non-lipidated APOE4.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2021)
Article
Chemistry, Multidisciplinary
Jing-Ming Shi, Hai-Yun Li, Hang Liu, Li Zhu, Yi-Bo Guo, Jie Pei, Hao An, Yan-Song Li, Sha-Di Li, Ze-Yu Zhang, Yi Zheng
Summary: Alzheimer's disease is associated with distinct amyloid-beta peptide (Aβ) assemblies, and the aggregation and neurotoxicity of Aβ depend on the N-terminal amino acid residues. The study found that N-terminal mutational peptides of Aβ42, including Aβ42(R5G), Aβ42(Y10F), and rat Aβ42, formed diffusible ligand, protofibrils, and fibrils that were indistinguishable by conventional techniques. However, the amyloid fibrillation was greatly inhibited in vitro. The results suggest that the N-terminus of Aβ is important for its fibrillation and neurotoxicity.
Meeting Abstract
Biophysics
Kaho Long, Thomas L. Williams, Brigita Urbanc
BIOPHYSICAL JOURNAL
(2019)
Meeting Abstract
Biophysics
Shuting Zhang, Cuong Trinh, Reinhard Schweitzer-Stenner, Brigita Urbanc
BIOPHYSICAL JOURNAL
(2019)
Article
Biochemistry & Molecular Biology
Kaho Long, Thomas L. Williams, Brigita Urbanc
Article
Chemistry, Physical
Shuting Zhang, Reinhard Schweitzer-Stenner, Brigita Urbanc
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2020)
Correction
Chemistry, Physical
Shuting Zhang, Reinhard Schweitzer-Stenner, Brigita Urbanc
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2020)
Article
Biochemistry & Molecular Biology
Brian Andrews, Shuting Zhang, Reinhard Schweitzer-Stenner, Brigita Urbanc
Article
Biophysics
Bridget Milorey, Reinhard Schweitzer-Stenner, Brian Andrews, Harald Schwalbe, Brigita Urbanc
Summary: Research indicates that charged amino acids play a significant role in protein conformation, stabilizing extended structures through interactions with neighboring residues. This study reveals the impact of charged arginine residues on the conformational preferences of peptides and proteins, supporting theoretical predictions regarding the structural behavior of polypeptides with high net charges.
BIOPHYSICAL JOURNAL
(2021)
Article
Chemistry, Physical
Brigita Urbanc
Summary: Recent studies suggest that Aβ oligomers may play a role in the protection and repair of the central nervous system, in addition to their toxicity in Alzheimer's disease. The focus is on the oxidative-stress-induced stabilization of Aβ oligomers via cross-linking, elucidating their structure, and potential inhibition of their toxicity.
JOURNAL OF PHYSICAL CHEMISTRY B
(2021)
Article
Chemistry, Physical
Shuting Zhang, Brian Andrews, Reinhard Schweitzer-Stenner, Brigita Urbanc
JOURNAL OF PHYSICAL CHEMISTRY B
(2020)
Article
Chemistry, Physical
Brian Andrews, Kaho Long, Brigita Urbanc
Summary: The study revealed that CHARMM36m better simulated the experimental observations of HP36 monomer populations at lower concentrations, but overly promoted protein aggregation at higher concentrations, while Amber ff14SB showed higher monomer populations and dissociation constants. Additionally, the water model plays a critical role in addressing the protein solubility problem in MD simulations.
JOURNAL OF PHYSICAL CHEMISTRY B
(2021)
Article
Chemistry, Physical
Brian Andrews, Jose Guerra, Reinhard Schweitzer-Stenner, Brigita Urbanc
Summary: Molecular dynamics is a powerful tool for studying intrinsically disordered proteins, but its reliability depends on the accuracy of the force field. This study evaluates the performance of several force fields in capturing conformational dynamics of guest residues in peptides and finds that the Gaussian model outperforms all MD force fields. The weaknesses of MD force fields include insufficient variability of certain residue populations, oversampling of certain secondary structures, inadequate sampling of certain conformations, and lack of residue-specificity in the Ramachandran distributions.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2022)
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
Biochemistry & Molecular Biology
Reinhard Schweitzer-Stenner, Raghed Kurbaj, Nichole O'Neill, Brian Andrews, Riya Shah, Brigita Urbanc
Summary: Disordered protein segments called SLiMs serve as recognition sites for biological processes and have various functions. Through spectroscopic methods, the conformational changes between two SLiM motifs were studied, and it was found that interactions between residues resulted in structural transitions. Increasing temperature led to a higher population of β-strand structures and a lower population of polyproline II structures.
Meeting Abstract
Biophysics
Bridget Milorey, Reinhard Schweitzer-Stenner, Brian Andrews, Harald Schwalbe, Brigita Urbanc
BIOPHYSICAL JOURNAL
(2021)
Meeting Abstract
Biophysics
Shuting Zhang, Reinhard Schweitzer-Stenner, Brigita Urbanc
BIOPHYSICAL JOURNAL
(2020)
Article
Biochemistry & Molecular Biology
Ankita Chadda, Alexander G. Kozlov, Binh Nguyen, Timothy M. Lohman, Eric A. Galburt
Summary: In this study, it was found that the DNA damage response in Mycobacterium tuberculosis differs from well-studied model bacteria. The DNA repair helicase UvrD1 in Mtb is activated through a redox-dependent process and is closely associated with the homo-dimeric Ku protein. Additionally, Ku protein is shown to stimulate the helicase activity of UvrD1.
JOURNAL OF MOLECULAR BIOLOGY
(2024)