Unveiling Neuroprotective Effects of a Triazole‐Based Compound in SH‐SY5Y Alzheimer's Disease‐Induced Cell Model

Abstract

This study presents a novel triazole‐based compound as a highly promising therapeutic agent against Alzheimer's disease (AD), specifically targeting amyloid beta (A β ) toxicity in neuronal cells. Using a comprehensive blend of advanced spectroscopy, microscopy, and mass spectrometry techniques, we demonstrate that this compound effectively inhibits A β peptide oligomerization, a well‐established primary driver of AD pathology. Crucially, high‐resolution mass spectrometry reveals the compound's selective affinity for distinct, highly toxic oligomeric populations, particularly tetramers and pentamers. These specific intermediate structures are abundant during the A β misfolding pathway and play a pivotal role in driving severe neurodegeneration. By disrupting the formation of these early‐stage toxic structures, the compound neutralizes their detrimental effects, limits amyloid accumulation, and actively promotes overall neuronal health. Furthermore, comprehensive molecular modeling analysis identifies acetylcholinesterase (AChE) as the primary macromolecular target for the observed drug action, suggesting a powerful multifaceted mechanism. By successfully mitigating A β ‐induced neurodegeneration and targeting AChE, this research underscores the immense potential of triazole‐based scaffolds in AD drug discovery. Ultimately, these findings highlight the therapeutic value of selectively halting A β oligomerization, offering molecular insights that pave the way for innovative, disease‐modifying treatments.