Acrylamide‐induced autophagy‐lysosomal pathway dysfunction contributing to neurotoxicity through targeting transcription factor EB

Autophagy-lysosomal pathway (ALP), a lysosome-mediated self-renewal process, is crucial for cell survival and death. Acrylamide (AA) neurotoxic compound produced during food thermal processing, the mechanism underlying AA-induced neurotoxicity remains elusive. In this study, we explored whether dysregulated ALP was involved in mechanism. We first evaluated toxic effects of AA on activation apoptosis NLRP3 human glioma U251 cells. found that autophagy with accumulation an substrate P62, which implies occurrence autophagy-lysosomal disorders. By using agonist PP242 siRNA interfering ATG5, demonstrated dysregulation contributed to inflammasome activation. addition, triggered dysfunction by decreasing expression transcription factor EB (TFEB), TFEB overexpression restored lysosomal-associated proteins protected against Moreover, rapamycin upregulating prevented neurotoxicity. Overall, our study provides novel insights into role disrupted highlights can be developed as promising intervention target