Article
Environmental Sciences
Samal Kaumbekova, Mehdi Amouei Torkmahalleh, Dhawal Shah
Summary: It is hypothesized that airborne particulate matter and ultrafine particles can influence the early onset and progression of Alzheimer's disease by impacting the aggregation of amyloid beta peptides. Molecular dynamics simulations revealed that ultrafine particles affected the aggregation of Aβ(16-21) peptides differently based on the type of ions present in the simulation environment. The presence of certain ions such as SO4-2 and NO3- accelerated the aggregation of Aβ(16-21) peptides in the presence of C-60, while NH4+ ions decelerated their aggregation.
ENVIRONMENTAL POLLUTION
(2021)
Article
Environmental Sciences
Samal Kaumbekova, Mehdi Amouei Torkmahalleh, Dhawal Shah
Summary: Long-term exposure to ambient ultrafine particles increases the risk of neurodegenerative diseases like Alzheimer's disease. This study used molecular dynamics simulations to investigate the effect of polycyclic aromatic hydrocarbons (PAHs) on the formation of A beta(42) oligomers. It was found that a specific PAH, Benzo[a]Pyrene (B[a]P), accelerated the formation of oligomers, while other concentrations of B[a]P suppressed the oligomerization process.
Article
Chemistry, Physical
Lorena Roldan-Martin, Francesca Peccati, Giuseppe Sciortino, Mariona Sodupe, Jean-Didier Marechal
Summary: Metal ions are important in the formation of beta-amyloid plaques in Alzheimer's disease, with Cu(ii) increasing alpha-helix content while Al(iii) decreases helical content and favors the appearance of transitory beta-strands in Aβ(42) conformation.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2021)
Article
Biochemistry & Molecular Biology
Nan Yuan, Lianmeng Ye, Yan Sun, Hao Wu, Zhengpan Xiao, Wanmeng Fu, Zuqian Chen, Yechun Pei, Yi Min, Dayong Wang
Summary: The major pathological feature of Alzheimer's disease (AD) is the aggregation of amyloid beta peptide (A beta) in the brain. Inhibition of A beta(42) aggregation may prevent the advancement of AD. This study found that arginine dipeptide (RR) was the most effective at interfering with A beta(42) polymerization and reducing its toxicity, including cell death, reactive oxygen species (ROS) production, and apoptosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Angelo Santoro, Manuela Grimaldi, Michela Buonocore, Ilaria Stillitano, Anna Maria D'Ursi
Summary: This study utilized NMR to analyze the conformational transition of A beta(1-42) in 50/50 HFIP/water, revealing unexpected routes in the evolution from helical to beta-sheet structures. Molecular dynamics simulations confirmed that the structural model calculated in this study is a starting point for amyloid fibrils formation.
Article
Biochemical Research Methods
Apneet Kaur, Bhupesh Goyal
Summary: Alzheimer's disease is a neurodegenerative disease characterized by accumulation of amyloid-beta (Aβ) peptide. This study designed and evaluated a library of 912 pentapeptides based on RIIGL for their potential to inhibit Aβ(42) aggregation using computational techniques. The pentapeptides RLAPV, RVVPI, and RIAPA showed higher binding affinity to Aβ(42) monomer compared to RIIGL, and they also prevented conformational conversion and destabilized crucial salt bridge in Aβ(42) monomer, leading to lower aggregation tendency.
JOURNAL OF MOLECULAR GRAPHICS & MODELLING
(2023)
Article
Biochemistry & Molecular Biology
Elena Ermakova, Olga Makshakova, Rauf Kurbanov, Ilya Ibraev, Yuriy Zuev, Igor Sedov
Summary: Uperin 3.5, a natural peptide from the skin of toadlets, consisting of 17 amino acids, possesses antimicrobial and amyloidogenic properties. Molecular dynamics simulations reveal that Uperin 3.5 and its mutants undergo spontaneous aggregation, transitioning from random coils to β-rich structures. The initial and crucial step in the aggregation process involves peptide dimerization and the formation of small β-sheets. The mutant peptides exhibit increased aggregation rate due to decreased positive charge and increased hydrophobic residues.
Article
Biochemistry & Molecular Biology
Trung Hai Nguyen, Phuong H. Nguyen, Son Tung Ngo, Philippe Derreumaux
Summary: This study investigates the role of cholesterol in the formation of aggregates of the A beta peptide, which is associated with Alzheimer's disease. The researchers find that cholesterol acts as a glue to speed up the formation of larger aggregates, providing a mechanistic link between cholesterol and the disease.
Article
Biochemistry & Molecular Biology
Phujinn Honorio, Supawadee Sainimnuan, Supa Hannongbua, Patchreenart Saparpakorn
Summary: The research discovered that protoberberine alkaloids isolated from natural resources are potent inhibitors of acetylcholinesterase (AChE) and have the potential to reduce symptoms of Alzheimer's disease. The key interactions of palmatine and berberine with AChE were identified as 7C-7C interactions with specific amino acids and H-bond interactions. In contrast, cyclanoline showed a different binding mode and preference for a deeper site within AChE.
CHEMICO-BIOLOGICAL INTERACTIONS
(2021)
Article
Biochemistry & Molecular Biology
Hadi Nedaei, Nasrollah Rezaei-Ghaleh, Karin Giller, Stefan Becker, Leila Karami, Ali Akbar Moosavi-Movahedi, Christian Griesinger, Ali Akbar Saboury
Summary: Alzheimer's disease is characterized by the presence of extraneuronal amyloid plaques composed of amyloid-beta (A beta) fibrillar aggregates in the brains of patients. Previous research has shown that atorvastatin, a cholesterol-lowering drug, can decrease the production of cerebral A beta in mouse models. This study explores the direct effect of atorvastatin on A beta 42 aggregation and finds that it promotes aggregation, likely due to the presence of calcium ions. However, this effect can be reversed by removing calcium ions.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Satoru Itoh, Hisashi Okumura
Summary: Aggregates of amyloid-beta (Aβ) peptides are enhanced at hydrophilic-hydrophobic interfaces and inhibited by polyphenols. Aβ40 accelerates aggregation due to its beta-hairpin structure, while polyphenols inhibit Aβ(16-22) aggregation by forming hydrogen bonds.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Phuong H. Nguyen, Philippe Derreumaux
Summary: The interactions between amyloid proteins and membranes have been extensively studied. Recent simulations have focused on the adsorption and insertion modes of amyloid-beta and tau proteins in membranes, aiming to design drugs that target the transient oligomers in Alzheimer's disease.
Article
Multidisciplinary Sciences
Myungwoon Lee, Wai-Ming Yau, John M. Louis, Robert Tycko
Summary: The study finds that A beta 42 fibrils exhibit polymorphism and have different molecular structures. Two qualitatively different structures of A beta 42 fibrils are reported using cryo-EM methods, derived from AD brain tissue. These results demonstrate a greater range of structural variations in A beta 42 fibrils than seen in previous studies.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Muthu Kumar Thirunavukkarasu, Ramanathan Karuppasamy
Summary: The study screened a candidate with high binding affinity in MEK protein from a library of 11,808 compounds, and suggested that Nebivolol may be an excellent candidate for MEK inhibition in NSCLC patients in the future.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Biochemistry & Molecular Biology
Sain Singh, Govinda R. Navale, Sonia Agrawal, Haobam Kisan Singh, Labhini Singla, Dhiman Sarkar, Manabendra Sarma, Anghuman Roy Choudhury, Kaushik Ghosh
Summary: Misfolding and aggregation of proteins are associated with neurodegenerative disorders. This study synthesized novel ruthenium complexes and investigated their inhibitory activity against protein aggregation and amyloid formation. The complexes showed significant inhibition of protein aggregation and amyloid fibril formation.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)