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Visualizing Axonal Growth Cone Collapse and Early Amyloid β Effects in Cultured Mouse Neurons
06:23

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Published on: October 30, 2018

Amyloid β-induced FOXRED2 mediates neuronal cell death via inhibition of proteasome activity

SangMi Shim1, WonJae Lee, HaeWon Chung

  • 1Creative Research Initiative (CRI)-Acceleration Research Laboratory, School of Biological Science/Bio-MAX Institute, Seoul National University, 599 Gwanak-ro, Gwanak-gu, Seoul, Korea.

Cellular and Molecular Life Sciences : CMLS
|October 26, 2010
PubMed

Insights

Amyloid-beta (Aβ) up-regulates FOXRED2, a protein that inhibits proteasome activity and assembly. This contributes to Aβ neurotoxicity through endoplasmic reticulum (ER) stress.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Biochemistry

Background:

  • Proteasome inhibition is implicated in amyloid-beta (Aβ)-induced neurotoxicity.
  • The endoplasmic reticulum (ER) plays a critical role in cellular homeostasis and stress responses.

Purpose of the Study:

  • To investigate the role of the novel ER-resident protein FOXRED2 in Aβ neurotoxicity.
  • To elucidate the mechanism by which FOXRED2 affects proteasome activity and contributes to neuronal cell death.

Main Methods:

  • Over-expression and down-regulation of FOXRED2 in rat cortical neurons and SH-SY5Y cells.
  • Assessing proteasome activity using microsomal fractions, gel filtration, and native gel electrophoresis.
  • Analyzing ER stress markers and cell death pathways, including caspase-12.

Main Results:

  • Aβ up-regulates FOXRED2 expression in neuronal cells.
  • FOXRED2 overexpression inhibits proteasome activity and assembly, while its reduction rescues proteasome function.
  • FOXRED2 triggers ER stress-mediated cell death via caspase-12, which can be attenuated by Salubrinal.

Conclusions:

  • Up-regulated FOXRED2 contributes to Aβ neurotoxicity by inhibiting proteasome assembly and inducing ER stress.
  • Targeting FOXRED2 may offer a therapeutic strategy for Aβ-related neurodegenerative diseases.

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