| First Author | Peng CX | Year | 2013 |
| Journal | Neurobiol Aging | Volume | 34 |
| Issue | 6 | Pages | 1555-63 |
| PubMed ID | 23402899 | Mgi Jnum | J:203363 |
| Mgi Id | MGI:5526894 | Doi | 10.1016/j.neurobiolaging.2012.12.010 |
| Citation | Peng CX, et al. (2013) Disease-modified glycogen synthase kinase-3beta intervention by melatonin arrests the pathology and memory deficits in an Alzheimer's animal model. Neurobiol Aging 34(6):1555-63 |
| abstractText | The current therapies for Alzheimer's disease (AD) are merely palliative that cannot arrest the pathologic progression of the disease. Therefore, it is critical to develop treatments that can target the disease-modifying molecule(s). In the present study, we found that treatment of tg2576 mice with melatonin from 4-8 months of age did not improve the pathology or behavioral performance of the mice. However, remarkable attenuation of tau and beta-amyloid pathologies with memory improvement were observed when melatonin was supplied from the age of 8-12 months or 4-12 months of the mice; more importantly, the improvements were still significant when the mice survived to old age. We also found that the disease stage-specific alteration of glycogen synthase kinase-3beta (GSK-3beta) but not protein phosphatase-2A, was correlated with the alterations of the pathology and behavior, and the timely targeting of GSK-3beta was critical for the efficacy of melatonin. Our finding suggests that melatonin treatment only at proper timing could arrest AD by targeting the activated GSK-3beta, which provides primary evidence for the importance and strategy in developing disease-modifying interventions of AD. |
