| First Author | Jia YL | Year | 2023 |
| Journal | Biochem Biophys Res Commun | Volume | 658 |
| Pages | 36-43 | PubMed ID | 37018887 |
| Mgi Jnum | J:335276 | Mgi Id | MGI:7468345 |
| Doi | 10.1016/j.bbrc.2023.02.076 | Citation | Jia YL, et al. (2023) The mitochondria-targeted small molecule SS31 delays progression of behavioral deficits by attenuating beta-amyloid plaque formation and mitochondrial/synaptic deterioration in APP/PS1 mice. Biochem Biophys Res Commun 658:36-43 |
| abstractText | Alzheimer's disease (AD) is a common neurodegenerative disorder characterized by progressive cognitive dysfunction and an impaired ability to carry out daily life functions. Mitochondrial dysfunction and beta-amyloid (Abeta) deposition are the most common causes of AD. Antioxidants have been shown to delay brain aging and AD development; however, it remains unknown whether the antioxidant peptide SS31 can protect mitochondrial and synaptic function and delay the progression of behavioral deficits in early-stage AD in vivo. Therefore, in this study we compared mitochondrial and synaptic changes, as well as the protective effects of SS31, in APP/PS1 transgenic mice and C57BL/6J control mice. The APP/PS1 transgenic mice exhibited elevated expression of Abeta40/Abeta42 and mitochondrial fission protein DLP1 and reduced expression of synaptophysin (SYN) and postsynaptic density protein 95 (PSD95) reductions, as well as increased levels of neuronal apoptosis and ROS in the hippocampus, and long-term treatment with SS31 reversed these effects. Furthermore, the cognitive impairments observed in APP/PS1 transgenic mice were reversed by SS31 treatment. Our findings show that SS31 lowers ROS and Abeta levels, protecting mitochondrial homeostasis and synaptic integrity, and ultimately improving behavioral deficits in early-stage AD. This suggests that SS31 is a potential pharmacological agent for treating or slowing the progression of AD. |
