Amyloid Beta Aggregation Mechanism

Alzheimer’s disease (AD) is a highly debilitating pathological condition directly related to the abnormal aggregation of misfolded amyloidogenic proteins. The amyloid hypothesis proposes amyloid β (Aβ) peptide as the main cause of the AD. The neurodegenerative disorders arise from the abnormal protein aggregation in the nervous tissue leading to intracellular inclusions or extracellular aggregates in specific brain areas. A feasible strategy to prevent the resulting neurodegeneration is based on the development of anti-amyloid molecules, i.e., those capable of preventing the generation of toxic aggregates. To address this issue, it’s extremely important to shed light on the molecular interactions responsible for protein aggregation. Despite substantial research efforts in this field, the fundamental mechanisms of protein misfolding and aggregation mechanisms remain somewhat unrevealed. In this context, computational molecular modelling represents a powerful tool in connecting macroscopic experimental findings to nanoscale molecular events

Figure: Amyloid beta aggregation mechanism.


  • Errico, G. Lucchesi, D. Odino, S. Muscat, C. Capitini, C. Bugelli, C. Canale, R. Ferrando, G. Grasso, D. Barbut, M. Calamai, A. Danani, M. Zasloff, A. Realini, G. Caminati, M. Vendruscolo, F. Chiti, “Making biological membrane resistant to the toxicity of misfolded protein oligomers: a lesson from trodusquemine”,Nanoscale, 2020, 1222596-22614, DOI: 10.1039/D0NR05285J
  • Grasso, A. Danani, “Molecular Simulations of Amyloid Beta Assemblies “, Advances in Physics: X, 5:1, 1770627, DOI:10.1080/23746149.2020.1770627
  • Muscat, L. Pallante, F. Stojceski, A. Danani, G. Grasso, M. A. Deriu, “The Impact of Natural Compounds on S-Shaped Aβ42 Fibril: from Molecular Docking to Biophysical Characterization”, Int. J. Mol. Sci. (2020) 21, 2017; DOI: 10.3390/ijms21062017
  • Muscat, F. Stojcevski, A. Danani, “Elucidating the Effect of Static Electric Field on Amyloid Beta 1-42 Supramolecular Assembly”, Journal of Molecular Graphics and Modelling (2020) May; 96: 107535; DOI: 10.1016/j.jmgm.2020.107535
  • Grasso, L. Leanza, U. Morbiducci, A. Danani, M.A. Deriu, “Aminoacid Substitutions in the Glycine Zipper Affect the Conformational Stability of Amyloid Beta Fibrils”,Journal of Biomolecular Structure and Dynamics, September 2019, DOI: 10.1080/07391102.2019.1671224
  • Grasso, M. Rebella, U. Morbiducci, J. A. Tuszynski, A. Danani, M.A Deriu, “The Role of Structural Polymorphism in Driving the Mechanical Performance of the Alzheimer’s Beta Amyloid Fibrils”, Frontiers in Bioengineering and Biotechnology,  April 2019DOI 10.3389/fbioe.2019.00083
  • Dal Magro, S. Simonelli, A. Cox , R. Corti , V. Cassina , L. Nardo , F. Mantegazza , G. Grasso , M.A. Deriu, A. Danani, L. Calabresi and F.Re, “The extent of human apolipoprotein A-I lipidation strongly affects the beta amyloid efflux across the blood-brain barrier in vitro”, Frontiers in Neuroscience,2019, 13 (419), DOI: 10.3389/fnins.2019.00419
  • Grasso, M. Rebella, S. Muscat, U. Morbiducci, J. A. Tuszynski, A. Danani, M.A Deriu, “Conformational Dynamics and Stability of U-Shaped and S-Shaped Amyloid Beta Oligomers”, International Journal of Molecular Sciences, February 2018, 19(2), DOI:10.3390/ijms19020571

Back to Research ongoing