| First Author | Izumi H | Year | 2018 |
| Journal | Neuroscience | Volume | 377 |
| Pages | 87-97 | PubMed ID | 29510211 |
| Mgi Jnum | J:262428 | Mgi Id | MGI:6158818 |
| Doi | 10.1016/j.neuroscience.2018.02.031 | Citation | Izumi H, et al. (2018) The Disease-modifying Drug Candidate, SAK3 Improves Cognitive Impairment and Inhibits Amyloid beta Deposition in App Knock-in Mice. Neuroscience 377:87-97 |
| abstractText | Alzheimer's disease (AD) is a progressive neurodegenerative disease and the most common form of elderly dementia in the world. At present, acetylcholine inhibitors, such as donepezil, galantamine and rivastigmine, are used for AD therapy, but the therapeutic efficacy is limited. We recently proposed T-type voltage-gated Ca(2+) channels' (T-VGCCs) enhancer as a new therapeutic candidate for AD. In the current study, we confirmed the pharmacokinetics of SAK3 in the plasma and brain of mice using ultra performance liquid chromatography-tandem mass spectrometry. We also investigated the effects of SAK3 on the major symptoms of AD, such as cognitive dysfunction and amyloid beta (Abeta) accumulation, in App(NL-F) knock-in (NL-F) mice, which have been established as an AD model. Chronic SAK3 (0.5mg/kg/day) oral administration for 3months from 9months of age improved cognitive function and inhibited Abeta deposition in 12-month-old NL-F mice. Using microarray and real-time PCR analysis, we discovered serum- and glucocorticoid-induced protein kinase 1 (SGK1) as one of possible genes involved in the inhibition of Abeta deposition and improvement of cognitive function by SAK3. These results support the idea that T-VGCC enhancer, SAK3 could be a novel candidate for disease-modifying therapeutics for AD. |
