Charge Modification of Lysine Mitigates Amyloid-β Aggregation.

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative condition characterized by the deposition of amyloid-β (Aβ) peptides, which aggregate into toxic structures such as oligomers, fibrils, and plaques. The presence of these Aβ aggregates in the brain plays a crucial role in the pathophysiology, leading to synaptic dysfunction and cognitive impairment. Understanding how physiological factors affect Aβ aggregation is essential, and therefore, exploring their influence in vitro will likely provide insights into their role in AD pathology. In this study, we investigated the effects of physiological, free amino acids on Aβ aggregation dynamics. We focused on positively charged amino acids, particularly lysine, and employed a chemical modification, methylation, to neutralize its charge. Our analyses revealed that modified lysine significantly reduced Aβ aggregation, indicating that charge distribution of amino acids plays a crucial role in modulating Aβ aggregation behavior. These findings enhance our understanding of the regulatory factors influencing Aβ aggregation and highlight important considerations for future research on Aβ.