LAUSR.org creates dashboard-style pages of related content for over 1.5 million academic articles. Sign Up to like articles & get recommendations!

Multipronged Regulatory Functions of Serum Albumin in Early Stages of Amyloid-β Aggregation.

Photo by bermixstudio from unsplash

Human serum albumin (HSA) is a major interacting-partner of Alzheimer's amyloid-β (Aβ) peptide in the plasma and has emerged as a promising therapeutic target. HSA inhibits Aβ fibrillization, but the… Click to show full abstract

Human serum albumin (HSA) is a major interacting-partner of Alzheimer's amyloid-β (Aβ) peptide in the plasma and has emerged as a promising therapeutic target. HSA inhibits Aβ fibrillization, but the underlying molecular mechanism is not well elucidated. In this work, we investigated the role of HSA in the early stages of Aβ aggregation by simulating the binding process of multiple Aβ monomers and protofibrils to HSA with extensive molecular dynamics simulations. HSA could simultaneously trap multiple Aβ monomers and accommodate the formation of nonfibrillar Aβ oligomers after binding. In particular, domains I and III show stronger binding capacities and hold preferable interaction sites for oligomers. Consequently, HSA prevents the formation of fibrillar oligomers in water, thus interfering with the nucleation process. On the other aspect, when protofibrils are preformed, HSA tends to block the β-strand spanning the central hydrophobic core located at the protofibril end, preventing the addition of monomers to protofibrils. Furthermore, Aβ protofibril structures are severely disrupted both globally and locally. Thus, further growth of protofibrils to fibrils is impeded by HSA. Our results collectively indicate that HSA performs multipronged regulatory functions in the early stages of Aβ aggregation. Our work advances the understanding of the amyloid inhibition of Aβ by HSA and provides theoretical guidance for developing rational therapies of Alzheimer's disease.

Keywords: multipronged regulatory; aggregation; regulatory functions; hsa; early stages; serum albumin

Journal Title: ACS chemical neuroscience
Year Published: 2021

Link to full text (if available)


Share on Social Media:                               Sign Up to like & get
recommendations!

Related content

More Information              News              Social Media              Video              Recommended



                Click one of the above tabs to view related content.