Related Experiment Video

Updated: Jun 8, 2026

Nuclear Magnetic Resonance Spectroscopy for the Identification of Multiple Phosphorylations of Intrinsically Disordered Proteins
12:47

Nuclear Magnetic Resonance Spectroscopy for the Identification of Multiple Phosphorylations of Intrinsically Disordered Proteins

Published on: December 27, 2016

Manganese induces tau hyperphosphorylation through the activation of ERK MAPK pathway in PC12 cells

Tongjian Cai1, Honglei Che, Ting Yao

  • 1Department of Occupational and Environmental Health, School of Public Health, Fourth Military Medical University, Xi'an 710032, China.

Toxicological Sciences : an Official Journal of the Society of Toxicology
|October 13, 2010
PubMed

Insights

Manganese exposure causes tau hyperphosphorylation, a key factor in neurodegenerative diseases. This process involves the activation of extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) pathways.

Area of Science:

  • Neuroscience
  • Toxicology
  • Cell Biology

Background:

  • Manganese is a known neurotoxicant linked to neurological disorders.
  • Hyperphosphorylated tau protein is implicated in neurodegenerative diseases.
  • The role of tau hyperphosphorylation in manganese neurotoxicity is not well understood.

Purpose of the Study:

  • To investigate the effect of manganese on tau phosphorylation in PC12 cells.
  • To elucidate the molecular mechanisms underlying manganese-induced neurotoxicity, focusing on tau pathology.

Main Methods:

  • PC12 cells were treated with manganese.
  • Western blot analysis was used to detect tau phosphorylation levels.
  • The involvement of extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) and glycogen synthase kinase-3β (GSK-3β) was assessed using specific inhibitors and Western blotting.

Main Results:

  • Manganese treatment significantly increased tau phosphorylation at multiple sites (Ser199, Ser202, Ser396, Ser404).
  • Manganese exposure led to the activation of ERK MAPK and GSK-3β.
  • Inhibition of ERK MAPK partially reduced manganese-induced tau hyperphosphorylation and cytotoxicity.

Conclusions:

  • Manganese exposure induces tau hyperphosphorylation in PC12 cells.
  • The ERK MAPK signaling pathway plays a crucial role in manganese-induced tau hyperphosphorylation and neurotoxicity.
  • These findings suggest a novel mechanism for manganese neurotoxicity involving tau pathology.

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