Paraquat Treatment Compromises the Clearance of β-Amyloid and Tau Proteins and Induces Primary Hippocampal Neuronal Cell Death through HSP70, P20S, and TFEB Disruption

Chem Res Toxicol. 2021 May 17;34(5):1240-1244. doi: 10.1021/acs.chemrestox.0c00370. Epub 2020 Nov 6.

Abstract

The herbicide paraquat (PQ) induces hippocampal neuronal cell loss and cognitive dysfunction after one and repeated treatment. All the mechanisms involved in these effects are not well understood. Single and repeated PQ treatment increased Aβ and tau protein levels, through HSP70 and TFEB downregulation and proteasome 20S inhibition, producing cell death in primary hippocampal neurons associated with cognitive decline. Our results reveal the mechanisms through which PQ could induce the accumulation of abnormal proteins and neurodegeneration that could originate the cognitive decline produced by it and could help managing its degenerative effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Peptides / antagonists & inhibitors
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / antagonists & inhibitors
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism
  • Cell Death / drug effects
  • HSP70 Heat-Shock Proteins / antagonists & inhibitors
  • HSP70 Heat-Shock Proteins / metabolism
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Mice
  • Neurons / drug effects
  • Neurons / metabolism
  • Paraquat / pharmacology*
  • Proteasome Endopeptidase Complex / metabolism
  • tau Proteins / antagonists & inhibitors
  • tau Proteins / metabolism

Substances

  • Amyloid beta-Peptides
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • HSP70 Heat-Shock Proteins
  • Tcfeb protein, mouse
  • tau Proteins
  • Proteasome Endopeptidase Complex
  • Paraquat