The chemical oxidation of albumin affects its capability to bind amyloid beta 1-40 peptide and to inhibit its aggregation.

Abstract

Human Serum Albumin (HSA) is the most abundant protein in the human body, exerting vital antioxidant and carrier functions. Beyond its systemic roles, HSA is clinically employed as a therapeutic tear supplement to restore the ocular surface proteome in severe dry eye and corneal diseases. However, the functional integrity of HSA is frequently compromised by oxidative stress, a hallmark of several neurodegenerative proteinopathies. While elevated levels of oxidised HSA have been documented in the blood and cerebrospinal fluid of Alzheimer's Disease patients, similar oxidative modifications are implicated in the pathogenesis of glaucoma and Age-related Macular Degeneration, where amyloid-beta (Aβ) peptides deposition and impaired protein clearance drive disease progression. Despite these clinical correlations, the specific impact of oxidative damage on the ability of HSA to chaperone and interact with Aβ peptides remains poorly understood. In this work, we applied several different experimental techniques to study the effect of oxidation on HSA conformation and oligomeric state when Chloramine T (CT) and hydrogen peroxide in Metal Catalysed Oxidation (MCO) are employed. ThT aggregation studies confirmed that the two different oxidised forms of HSA affect Aβ1-40 fibrillation differently. In addition, SPR interaction studies between the two differently oxidised forms of HSA and Aβ1-40 allowed us to prove that CT and MCO induce two different oxidative damages on HSA, which in turn induce lower binding capability towards Aβ1-40. Our results indicate a possible explanation for the role of oxidised HSA in the development and progression of brain and retinal neurodegeneration characterized by accumulation of Aβ.