| First Author | Castro-Alvarez JF | Year | 2015 |
| Journal | J Neurosci Res | Volume | 93 |
| Issue | 8 | Pages | 1258-66 |
| PubMed ID | 25711385 | Mgi Jnum | J:286059 |
| Mgi Id | MGI:6390457 | Doi | 10.1002/jnr.23576 |
| Citation | Castro-Alvarez JF, et al. (2015) Cyclin-Dependent kinase 5 targeting prevents beta-Amyloid aggregation involving glycogen synthase kinase 3beta and phosphatases. J Neurosci Res 93(8):1258-66 |
| abstractText | Inappropriate activation of cyclin-dependent kinase 5 (CDK5) resulting from proteolytic release of the activator fragment p25 from the membrane contributes to the formation of neurofibrillary tangles, beta-amyloid (betaA) aggregation, and chronic neurodegeneration. At 18 months of age, 3x Tg-AD mice were sacrificed after either 3 weeks (short term) or 1 year (long term) of CDK5 knockdown. In short-term-treated animals, CDK5 knockdown reversed betaA aggregation in the hippocampi via inhibitory phosphorylation of glycogen synthase kinase 3beta Ser9 and activation of phosphatase PP2A. In long-term-treated animals, CDK5 knockdown induced a persistent reduction in CDK5 and prevented betaA aggregation, but the effect on amyloid precursor protein processing was reduced, suggesting that yearly booster therapy would be required. These findings further validate CDK5 as a target for preventing or blocking amyloidosis in older transgenic mice. |
