Presenilin-1 protects against neuronal apoptosis caused by its interacting protein PAG

Yan Zhou, Wanjiang Zhang, Rachael Easton, James W. Ray, Patricia Lampe, Zhihong Jiang, Anne L. Brunkan, Alison Goate, Eugene M. Johnson, Jane Y. Wu

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


Mutations in the presenilin-1 (PS-1) gene account for a significant fraction of familial Alzheimer's disease. The biological function of PS-1 is not well understood. We report here that the proliferation-associated gene (PAG) product a protein of the thioredoxin peroxidase family interacts with PS-1. Microinjection of a plasmid expressing PAG into superior cervical ganglion (SCG) sympathetic neurons in primary cultures led to apoptosis. Microinjection of plasmids expressing wild-type PS-1 or a PS-1 mutant with a deletion of exon 10 (PS1dE10) by themselves had no effect on the survival of primary SCG neurons. However co-injection of wild-type PS-1 with PAG prevented neuronal death whereas co-injection with the mutant PS-1 did not affect PAG-induced apoptosis. Furthermore overexpression of PAG accelerated SCG neuronal death induced by nerve growth factor deprivation. This sensitizing effect was also blocked by wild-type PS-1 but not by PS1dE10. These results establish an assay for studying the function of PS-1 in primary neurons reveal the neurotoxicity of a thioredoxin peroxidase demonstrate a neuroprotective activity of the wild-type PS-1 and suggest possible involvement of defective neuroprotection by PS-1 mutants in neurodegeneration.

Original languageEnglish (US)
Pages (from-to)126-138
Number of pages13
JournalNeurobiology of Disease
Issue number2
StatePublished - Mar 2002

ASJC Scopus subject areas

  • Neurology


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