Abstract
Alzheimer's disease (AD), a major neurodegenerative disorder, is characterized by the progressive accumulation of amyloid-β (Aβ) plaques, leading to cognitive decline. Despite the existing treatments, their limited efficacy highlights the urgent need for novel therapeutic strategies. The present study investigates the neuroprotective effects of a grape seed polyphenol extract (GSPE) on transgenic Caenorhabditis elegans models specifically expressing human Aβ proteins. The obtained results show that GSPE not only significantly attenuates Aβ-induced paralysis but also extends the lifespan and improves sensory responses in these models, suggesting improved neural function and overall health. Additionally, GSPE treatment reduces proteasomal activity, which could lead to a reduction in the accumulation of misfolded proteins. It also modulates the expression of key genes involved in autophagy and proteostasis, thereby enhancing cellular mechanisms to manage protein aggregation and combat oxidative stress. On the whole, these findings support the potential of grape seed procyanidins (the main components in the extract) to be used as an effective dietary approach to mitigate Alzheimer's disease pathology through the modulation of critical neuroprotective pathways.