| First Author | Guo Q | Year | 1999 |
| Journal | J Neurochem | Volume | 72 |
| Issue | 3 | Pages | 1019-29 |
| PubMed ID | 10037473 | Mgi Jnum | J:53132 |
| Mgi Id | MGI:1331317 | Doi | 10.1046/j.1471-4159.1999.0721019.x |
| Citation | Guo Q, et al. (1999) Increased vulnerability of hippocampal neurons from presenilin-1 mutant knock-in mice to amyloid beta-peptide toxicity: central roles of superoxide production and caspase activation. J Neurochem 72(3):1019-29 |
| abstractText | Many cases of early-onset inherited Alzheimer's disease (AD) are caused by mutations in the presenilin-1 (PSI) gene. Overexpression of PSI mutations in cultured PC12 cells increases their vulnerability to apoptosis-induced trophic factor withdrawal and oxidative insults. We now report that primary hippocampal neurons from PS1 mutant knock-in mice, which express the human PS1M146V mutation at normal levels, exhibit increased vulnerability to amyloid beta-peptide toxicity. The endangering action of mutant PSI was associated with increased superoxide production, mitochondrial membrane depolarization, and caspase activation. The peroxynitrite-scavenging antioxidant uric acid and the caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone protected hippocampal neurons expressing mutant PSI against cell death induced by amyloid beta-peptide. Increased oxidative stress may contribute to the pathogenic action of PSI mutations, and antioxidants may counteract the adverse property of such AD-linked mutations. |
