Journal of Molecular Neuroscience

, Volume 25, Issue 1, pp 79–94

Phospho-β-catenin accumulation in alzheimer’s disease and in aggresomes attributable to proteasome dysfunction

Original Article An Article Related To The 2004 Chemistry Nobel Prize

DOI: 10.1385/JMN:25:1:079

Cite this article as:
Ghanevati, M. & Miller, C.A. J Mol Neurosci (2005) 25: 79. doi:10.1385/JMN:25:1:079

Abstract

Accumulation of cytoplasmic inclusion bodies in many neurodegenerative diseases, including Alzheimer’s disease (AD), might result from dysfunction of the ubiquitin-proteasome system. This system degrades many cellular proteins, including β-catenin, a member of the Wnt signaling pathway, and a presenilin-1-interacting protein. Phosphorylation of β-catenin marks it for ubiquitination and rapid proteasomal degradation. We found phospho-β-catenin accumulated as detergent-insoluble, punctate, cytoplasmic inclusions in hippocampal pyramidal neurons more abundantly in AD than in aged controls. In AD, β-catenin was ubiquitin conjugated, thus suggesting impaired proteasome-dependent degradation. Phospho-β-catenin was partially sequestered within granulovacuolar degeneration bodies but not in lysosomes, indicating sequestration within autophagosomes. Exposure of neuronal cultures to proteasome inhibitors induced formation of detergent-insoluble, phospho-β-catenin-positive cytoplasmic inclusions that coalesced into aggresomes and colocalized with γ-tubulin and vimentin. These aggregates were associated with apoptotic cell death and with activation of caspase-3, c-Jun-N-terminal kinases, and c-Jun. These findings suggest that phospho-β-catenin accumulation in AD might result from impaired proteasome function.

Index Entries

Aggresome Alzheimer’s disease granulovacuolar degeneration phospho-β-catenin proteasome 

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Copyright information

© Humana Press Inc 2005

Authors and Affiliations

  1. 1.Department of PathologyUniversity of Southern CaliforniaLos Angeles
  2. 2.Department of NeurologyUniversity of Southern CaliforniaLos Angeles
  3. 3.Department of Program in Neuroscience, Keck School of MedicineUniversity of Southern CaliforniaLos Angeles

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