Par-4 is a mediator of neuronal degeneration associated with the pathogenesis of Alzheimer disease.
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 beta-protein (A beta) 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 withdrawal. Par-4 expression was enhanced, and mitochondrial dysfunction and apoptosis exacerbated, in cells expressing presenilin-1 mutations associated with early-onset inherited AD.
Guo
Q
Q
Sanders-Brown Research Center on Aging, University of Kentucky, Lexington 40536, USA.
Fu
W
W
Xie
J
J
Luo
H
H
Sells
S F
SF
Geddes
J W
JW
Bondada
V
V
Rangnekar
V M
VM
Mattson
M P
MP
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000096:biosynthesis / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D002352:Carrier Proteins / Q000032:analysis / Q000096:biosynthesis*; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D016350:Leucine Zippers; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D008928:Mitochondria / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D016716:PC12 Cells; D010446:Peptide Fragments / Q000096:biosynthesis / Q000494:pharmacology; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D053764:Presenilin-1; D011471:Prostatic Neoplasms / Q000473:pathology; D051381:Rats
D016229:Amyloid beta-Peptides; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D016376:Oligonucleotides, Antisense; C508853:PSEN1 protein, human; D010446:Peptide Fragments; D053764:Presenilin-1; C075222:amyloid beta-protein (1-42); C101296:prostate apoptosis response-4 protein