| First Author | Lo AC | Year | 2013 |
| Journal | Neuropharmacology | Volume | 75 |
| Pages | 458-66 | PubMed ID | 24035915 |
| Mgi Jnum | J:214494 | Mgi Id | MGI:5603042 |
| Doi | 10.1016/j.neuropharm.2013.08.030 | Citation | Lo AC, et al. (2013) Dose-dependent improvements in learning and memory deficits in APPPS1-21 transgenic mice treated with the orally active Abeta toxicity inhibitor SEN1500. Neuropharmacology 75:458-66 |
| abstractText | In the Alzheimer's disease (AD) brain, accumulation of Abeta1-42 peptides is suggested to initiate a cascade of pathological events. To date, no treatments are available that can reverse or delay AD-related symptoms in patients. In the current study, we introduce a new Abeta toxicity inhibitor, SEN1500, which in addition to its block effect on Abeta1-42 toxicity in synaptophysin assays, can be administered orally and cross the blood-brain barrier without adverse effects in mice. In a different set of animals, APPPS1-21 mice were fed with three different doses of SEN1500 (1 mg/kg, 5 mg/kg and 20 mg/kg) for a period of 5 months. Cognition was assessed in a variety of behavioral tests (Morris water maze, social recognition, conditioned taste aversion and passive avoidance). Results suggest a positive effect on cognition with 20 mg/kg SEN1500 compared to control APPPS1-21 mice. However, no changes in soluble or insoluble Abeta1-40 and Abeta1-42 were detected in the brains of SEN1500-fed mice. SEN1500 also attenuated the effect of Abeta1-42 on synaptophysin levels in mouse cortical neurons, which indicated that the compound blocked the synaptic toxicity of Abeta1-42. In vitro and in vivo effects presented here suggest that SEN1500 could be an interesting AD therapeutic. |
