The role of TFEB-mediated autophagy-lysosome dysfunction in manganese neurotoxicity

• Published in: Current research in toxicology Vol. 7; p. 100193
• Main Authors: Lu, Jiaqiao, Su, Peng, Zhao, Fang, Yu, Kailun, Yang, Xunbo, Lv, Hui, Wang, Diya, Zhang, Jianbin
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.01.2024; Elsevier
• Subjects: Autophagy; Lysosome; Manganese neurotoxicity; Research Paper; TFEB; TFEB; Manganese neurotoxicity; Autophagy; Lysosome
• ISSN: 2666-027X; 2666-027X
• DOI: 10.1016/j.crtox.2024.100193

[Display omitted] •Manganese exposure can induce abnormal autophagy function of neurons.•TFEB expression decrease is linked to abnormal lysosomal degradation.•Overexpression of TFEB in neurons can alleviate the neurotoxicity of manganese. Excessive long-term manganese intake can inflict irreversible damage to the nervous system, with a predominant effect on the substantia nigra-striatum pathway. Through a mouse model simulating manganese exposure, we delved into its implications on the central nervous motor system, uncovering autophagy-lysosome dysfunction as a pivotal factor in manganese-induced neurotoxicity. Our research illuminated the molecular mechanisms behind TFEB’s role in manganese-triggered neuronal autophagy dysfunction, offering insights into the cellular and molecular mechanisms of manganese-induced abnormal protein accumulation. This study lays a significant theoretical foundation for future endeavors aimed at safeguarding against manganese neurotoxicity. Furthermore, TFEB emerges as a potential early molecular biomarker for manganese exposure, providing a solid basis for preemptive protection and clinical treatment for populations exposed to manganese.