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

Jiaqiao Lu1, Peng Su1, Fang Zhao1

  • 1Department of Occupational and Environmental Health, the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, No.169 Chang Le West Rd., Xi'an, Shaanxi 710032, China.

Current Research in Toxicology
|October 9, 2024
PubMed

Insights

Excessive manganese exposure causes neurotoxicity by disrupting autophagy-lysosome pathways. Transcription Factor EB (TFEB) is identified as a key player and potential early biomarker for manganese exposure.

Area of Science:

  • Neuroscience
  • Toxicology
  • Cellular Biology

Background:

  • Long-term excessive manganese intake leads to irreversible nervous system damage, particularly affecting the substantia nigra-striatum pathway.
  • Manganese neurotoxicity is a growing concern, necessitating a deeper understanding of its underlying mechanisms.

Purpose of the Study:

  • To investigate the impact of manganese exposure on the central nervous motor system using a mouse model.
  • To elucidate the role of autophagy-lysosome dysfunction and Transcription Factor EB (TFEB) in manganese-induced neurotoxicity.

Main Methods:

  • Utilized a mouse model to simulate chronic manganese exposure.
  • Analyzed the molecular mechanisms of autophagy dysfunction and TFEB's involvement in manganese-exposed neuronal cells.

Main Results:

  • Autophagy-lysosome dysfunction was identified as a critical factor in manganese-induced neurotoxicity.
  • The study revealed TFEB's role in manganese-triggered neuronal autophagy dysfunction and abnormal protein accumulation.

Conclusions:

  • Manganese exposure disrupts neuronal autophagy via TFEB, contributing to neurotoxicity.
  • TFEB shows potential as an early molecular biomarker for manganese exposure, aiding in preemptive protection and clinical treatment strategies.
Keywords:
AutophagyLysosomeManganese neurotoxicityTFEB

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