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Carboxypeptidase E in neuroprotection: links to neurodegeneration and Alzheimer disease

Monday, October 24, 2011 — Poster Session I

Noon – 2:00 p.m.

Natcher Conference Center




  • Y Cheng
  • NX Cawley
  • T Yanik
  • CP Liu
  • A Papazian
  • SRK Murthy
  • PY Loh


A search with the nucleotide sequence of human CPE against the GeneBank EST database identified an EST entry from Alzheimer cortex tissue that had three adenosine inserts. This introduces 9 amino acids in the first beta-pleated sheet after the pro-domain of the mutant CPE protein. Expression studies demonstrated that it was made but failed to be secreted. It accumulated in the ER where it was targeted for degradation by the proteosome. Co-expression of WT and the mutant resulted in the degradation of both forms of the protein and reduction in the secretion of WT CPE. Expression in Neuro2a cells and rat hippocampal neurons resulted in ER stress induced cell death signaling as evidenced by the expression of CHOP and an increase in cytotoxicity and neuronal cell death as measured by LDH and MTT assays. We speculate that aged neurons expressing WT and mutant CPE may result in 1) a reduction in overall levels of CPE due to degradation initiated by the mutant and 2) may become more susceptible to ER stress-induced cell death leading to neuronal loss. This would result in the loss of the neuroprotective functions of CPE and possibly lead to neurodegenerative diseases including Alzheimer disease.

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