Sesamol as a potential small molecule in inhibiting the induction of neurotoxic amyloids fibrils involved in the pathophysiology of alzheimer's disease

The presence of possibly toxic forms of intracellular a-synuclein, binding of aggregated a-synuclein and monomeric Ab, and the potential co-localization of a-synuclein with intracellular neurofibrillary tangles as well as Ab plaques in the brain could be the main causes in serious clinical symptoms mostly developed in Alzheimer's disease (AD) patients. Amyloid formation of asynuclein can also induce neurotoxic effects through stimulation of endoplasmic reticulum stress (ERS). Therefore, the inhibition of protein aggregation can be of great importance for the control of pathophysiology of AD. Here, we assessed the use of sesamol as bioactive small molecule in inhibition of a-synuclein fibrillogenesis and neurotoxicity by different biophysical [ThT/Nile red/Congo red (CR)/circular dichroism (CD)] and cellular (MTT and qRT-PCR) analyses. From the spectroscopic analyses, we found that sesamol displays potential effect on the inhibiting the asynuclein fibril formation. Also, sesamol showed no significant neurotoxicity and co-incubation of a-synuclein with sesamol apparently mitigated the ERS-mediated apoptosis induced by asynuclein amyloids through regulation of IRE1, PERK, ATF6, and caspase-3 mRNA. Overall, sesamol-based compounds can be further developed and assessed for the regulation of pathophysiology of AD in which a-synuclein amyloids are predominantly involved. & COPY; 2023 The Authors. Published by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).