| First Author | Dong YT | Year | 2020 |
| Journal | Am J Pathol | Volume | 190 |
| Issue | 7 | Pages | 1545-1564 |
| PubMed ID | 32289286 | Mgi Jnum | J:348529 |
| Mgi Id | MGI:6819621 | Doi | 10.1016/j.ajpath.2020.03.015 |
| Citation | Dong YT, et al. (2020) Silent Mating-Type Information Regulation 2 Homolog 1 Attenuates the Neurotoxicity Associated with Alzheimer Disease via a Mechanism Which May Involve Regulation of Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha. Am J Pathol 190(7):1545-1564 |
| abstractText | To investigate the neuroprotective role of silent mating-type information regulation 2 homolog 1 (SIRT1) in Alzheimer disease (AD), brain tissues from patients with AD and APP/PS1 mice as well as primary rat neurons exposed to oligomers of amyloid-beta peptide were examined. The animals were treated with resveratrol (RSV) or suramin for 2 months. Cell cultures were treated with RSV, suramin, and the peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1alpha) stimulator ZLN005. Cells were transiently transfected with PGC-1alpha silencing RNA. The level of SIRT1 in brain tissues from patients with AD and APP/PS1 mice, including nuclear and mitochondrial proteins, as well as in primary neurons exposed to oligomers of amyloid-beta peptide, was decreased. Overexpression of APP/PS1 impaired learning and memory of mice; produced more senile plaques, disrupted membranes, and resulted in broken or absent cristae of mitochondria in the brain; decreased levels of A disintegrin and metallopeptidase domain 10, beta-secretase 2, 8-oxoguanine DNA glycosylase-1, PGC-1alpha, and NAD+; and increased levels of beta-secretase 1 and apoptosis. Interestingly, these changes were attenuated significantly by RSV treatment but enhanced by suramin administration. By activating PGC-1alpha but inhibiting SIRT1, apoptotic cell death was significantly decreased; however, by activating SIRT1 but inhibiting PGC-1alpha with small interfering PGC-1alpha, these levels remained unchanged. These findings indicate that SIRT1 may protect against AD-associated neurotoxicity, which might involve PGC-1alpha regulation. |
