Human albumin impairs amyloid β-peptide fibrillation through its C-terminus: From docking Modeling to protection against neurotoxicity in Alzheimer's disease

Publication date: Available online 26 June 2019Source: Computational and Structural Biotechnology JournalAuthor(s): Pol Picón-Pagès, Jaume Bonet, Javier García-García, Joan Garcia-Buendia, Daniela Gutierrez, Javier Valle, Carmen E.S. Gómez-Casuso, Valeriya Sidelkivska, Alejandra Alvarez, Alex Perálvarez-Marín, Albert Suades, Xavier Fernàndez-Busquets, David Andreu, Rubén Vicente, Baldomero Oliva, Francisco J. MuñozAbstractAlzheimer's disease (AD) is a neurodegenerative process characterized by the accumulation of extracellular deposits of amyloid β-peptide (Aβ), which induces neuronal death. Monomeric Aβ is not toxic but tends to aggregate into β-sheets that are neurotoxic. Therefore to prevent or delay AD onset and progression one of the main therapeutic approaches would be to impair Aβ assembly into oligomers and fibrils and to promote disaggregation of the preformed aggregate. Albumin is the most abundant protein in the cerebrospinal fluid and it was reported to bind Aβ impeding its aggregation. In a previous work we identified a 35-residue sequence of clusterin, a well-known protein that binds Aβ, that is highly similar to the C-terminus (CTerm) of albumin. In this work, the docking experiments show that the average binding free energy of the CTerm-Aβ1–42 simulations was significantly lower than that of the clusterin-Aβ1–42 binding, highlighting the possibility that the CTerm retains albumin's binding properties. To validate this observation, we per...
Source: Computational and Structural Biotechnology Journal - Category: Biotechnology Source Type: research