Journal ArticleDOI
Insights into the Inhibitory Mechanism of Dicyanovinyl‐Substituted J147 Derivative against Aβ42 Aggregation and Protofibril Destabilization: A Molecular Dynamics Simulation Study
Suniba Shuaib,Rajneet Kaur Saini,Deepti Goyal,Bhupesh Goyal +3 more
- Vol. 2, Iss: 4, pp 1645-1657
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The article was published on 2017-02-01. It has received 25 citations till now. The article focuses on the topics: Derivative (chemistry).read more
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Benzofuran and Indole: Promising Scaffolds for Drug Development in Alzheimer's Disease.
TL;DR: The history and recent advances of benzofuran‐ and indole‐based compounds as inhibitors of butyrylcholinesterase, acetylcholinerase, γ‐secretase, β‐ secretase, tau misfolding, and β‐amyloid aggregation are focused on.
Journal ArticleDOI
Molecular Simulations Reveal Terminal Group Mediated Stabilization of Helical Conformers in Both Amyloid-β42 and α-Synuclein.
TL;DR: Predict a common intrapeptide route to stabilization based on the plasticity of helical conformations of Aβ42 and αS as assessed through extensive atomistic molecular dynamics (MD) computer simulations across ten distinct protein force field and water model combinations.
Journal ArticleDOI
Conformational Dynamics and Stability of U-Shaped and S-Shaped Amyloid β Assemblies.
Gianvito Grasso,Martina Rebella,Stefano Muscat,Umberto Morbiducci,Jack A. Tuszynski,Jack A. Tuszynski,Andrea Danani,Marco Agostino Deriu +7 more
TL;DR: Computational results provide support for the stability of the recently proposed S-shaped model due to the maximized interactions involving the C-terminal residues, and suggest that the molecular architecture of the protein aggregates might play a pivotal role in formation and conformational Stability of the resulting fibrils.
Journal Article
Synthetic curcumin analogs as inhibitors of β -amyloid peptide aggregation
TL;DR: The ability of curcumin to attach to Aβ peptide and prevent its accumulation is attributed to its three structural characteristics such as the presence of two aromatic end groups and their co-planarity, the length and rigidity of the linker region and the substitution conformation of these aromatics as mentioned in this paper.
Journal ArticleDOI
Caffeine destabilizes preformed Aβ protofilaments: insights from all atom molecular dynamics simulations.
TL;DR: The atomistic details obtained via in silico studies relating to the mechanism behind the underlying destabilization of Aβ17-42 protofibrils by caffeine encourage further investigations exploring the potency of natural compounds to treat AD via disrupting preformed neurotoxic Aβ prot ofibrils.
References
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Alzheimer's Disease: Genes, Proteins, and Therapy
TL;DR: Evidence that the presenilin proteins, mutations in which cause the most aggressive form of inherited AD, lead to altered intramembranous cleavage of the beta-amyloid precursor protein by the protease called gamma-secretase has spurred progress toward novel therapeutics and provided discrete biochemical targets for drug screening and development.
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Calculating Structures and Free Energies of Complex Molecules: Combining Molecular Mechanics and Continuum Models
Peter A. Kollman,Irina Massova,Carolina M. Reyes,Bernd Kuhn,Shuanghong Huo,Lillian T. Chong,Matthew Lee,Tai-Sung Lee,Yong Duan,Wei Wang,Oreola Donini,Piotr Cieplak,Jaysharee Srinivasan,David A. Case,Thomas E. Cheatham +14 more
TL;DR: A historical perspective on the application of molecular dynamics to biological macromolecules is presented and recent developments combining state-of-the-art force fields with continuum solvation calculations have allowed for the fourth era of MD applications in which one can often derive both accurate structure and accurate relative free energies from molecular dynamics trajectories.
Journal ArticleDOI
Essential dynamics of proteins
TL;DR: Analysis of extended molecular dynamics simulations of lysozyme in vacuo and in aqueous solution reveals that it is possible to separate the configurational space into two subspace: an “essential” subspace containing only a few degrees of freedom and the remaining space in which the motion has a narrow Gaussian distribution and which can be considered as “physically constrained.”
Journal ArticleDOI
Curcumin Inhibits Formation of Amyloid β Oligomers and Fibrils, Binds Plaques, and Reduces Amyloid in Vivo
Fusheng Yang,Giselle P. Lim,Giselle P. Lim,Aynun N. Begum,Aynun N. Begum,Oliver J. Ubeda,Oliver J. Ubeda,Mychica Simmons,Mychica Simmons,Surendra S. Ambegaokar,Surendra S. Ambegaokar,Pingping P. Chen,Pingping P. Chen,Rakez Kayed,Charles G. Glabe,Sally A. Frautschy,Sally A. Frautschy,Gregory M. Cole,Gregory M. Cole +18 more
TL;DR: It is suggested that low dose curcumin effectively disaggregates Aβ as well as prevents fibril and oligomer formation, supporting the rationale forCurcumin use in clinical trials preventing or treating AD.
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The amyloid cascade hypothesis for Alzheimer's disease: an appraisal for the development of therapeutics.
TL;DR: It is timely to review the science underpinning the amyloid cascade hypothesis, consider what type of clinical trials will constitute a valid test of this hypothesis and explore whether amyloids-β-directed therapeutics will provide the medicines that are urgently needed by society for treating this devastating disease.