Effect of osmolytes on the conformational stability of Aβ(25–35): A circular dichroism analysis

Alzheimer's (AD) is a neurodegenerative disease characterized by the onset and progression of mental decline. AD aetiopathogenesis is still questioned; however, according to one of the most accredited hypotheses, the accumulation of amyloid plaques formed by aggregated Aβ peptides is the primary cause of neuronal function loss. Accordingly, hundreds of molecules have been screened for their possible action to prevent or destroy amyloid aggregates. Following this track, osmolytes, naturally occurring small molecules produced by several organisms in response to external stressors, were recently evaluated as modulators of Aβ aggregation. In this study, we examined the conformational stability of Aβ(25-35) when exposed to the osmolytes acetylcholine (ACh), succinylcholine (SCh), and betaine (Bet). Aβ(25-35) is the shortest fragment known for replicating the aggregation process seen in Aβ peptides. By collecting circular dichroism (CD) spectra in water and different membrane-mimicking systems, we investigated the potential of the mentioned osmolytes to stabilize the soluble conformations of Aβ(25-35) and preserve them from denaturing conditions. Our data suggest that Bet is a promising small molecule that can safeguard the soluble form of Aβ peptide and is effective in counteracting environmental conditions by favoring the amyloid aggregation associated with pathology progression.