Abstract
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 language | English (US) |
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Pages (from-to) | 126-138 |
Number of pages | 13 |
Journal | Neurobiology of Disease |
Volume | 9 |
Issue number | 2 |
DOIs | |
State | Published - Mar 2002 |
ASJC Scopus subject areas
- Neurology