RGD Reference Report - Presenilin-1 protects against neuronal apoptosis caused by its interacting protein PAG. - Rat Genome Database

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

Authors: Zhou, Y  Zhang, W  Easton, R  Ray, JW  Lampe, P  Jiang, Z  Brunkan, AL  Goate, A  Johnson, EM  Wu, JY 
Citation: Zhou Y, etal., Neurobiol Dis 2002 Mar;9(2):126-38.
RGD ID: 1304239
Pubmed: PMID:11895366   (View Abstract at PubMed)
DOI: DOI:10.1006/nbdi.2001.0472   (Journal Full-text)

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.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Psen1Ratnegative regulation of apoptotic process  IDA  RGD 
Psen1Ratnegative regulation of neuron apoptotic process  IMP  RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Psen1Ratincreased apoptosis  IDA  RGD 
Objects Annotated

Genes (Rattus norvegicus)
Psen1  (presenilin 1)

Additional Information