Journal
JOURNAL OF NEUROSCIENCE RESEARCH
Volume 93, Issue 8, Pages 1258-1266Publisher
WILEY-BLACKWELL
DOI: 10.1002/jnr.23576
Keywords
beta-amyloid plaques; GSK3 beta Ser9; PP2A; Alzheimer's disease; CDK5 RNAi
Categories
Funding
- Colciencias Projects [111545921503, 111551928905]
- FIC
- NIA [RO1-AG029802-01]
- NATIONAL INSTITUTE ON AGING [R01AG029802] Funding Source: NIH RePORTER
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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, -amyloid (A) 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 A aggregation in the hippocampi via inhibitory phosphorylation of glycogen synthase kinase 3 Ser9 and activation of phosphatase PP2A. In long-term-treated animals, CDK5 knockdown induced a persistent reduction in CDK5 and prevented A 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. (c) 2015 Wiley Periodicals, Inc.
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