Par-4 is a mediator of neuronal degeneration associated with the pathogenesis of Alzheimer disease

Qing Guo, Weiming Fu, Jun Xie, Hong Luo, Stephen F. Sells, J. W. Geddes, Vimala Bondada, Vivek M. Rangnekar, Mark P. Mattson

Research output: Contribution to journalArticlepeer-review

Abstract

Prostate apoptosis response-4 (Par-4) is a protein containing both a leucine zipper and a death domain that was isolated by differential screening for genes upregulated in prostate cancer cells undergoing apoptosis. Par-4 is expressed in the nervous system, where its function, is unknown. In Alzheimer disease (AD), neurons may die by apoptosis, and amyloid β-protein (Aβ) may play a role in this. We report here that Par-4 expression is increased in vulnerable neurons in AD brain and is induced in cultured neurons undergoing apoptosis. Blockade of Par-4 expression or function prevented neuronal apoptosis induced by Ab and trophic factor withdrawl. Par-4 expression was enhanced, and mitochondrial dysfunction and apoptosis exacerbated, in cells expressing presenilin-1 mutations associated with early-onset inherited AD.

Original languageEnglish (US)
Pages (from-to)957-962
Number of pages6
JournalNature Medicine
Volume4
Issue number8
DOIs
StatePublished - Aug 1998
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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