Abstract
CDK5 is a member of the cyclin-dependent kinase family with diverse functions in both the developing and mature nervous system. The inappropriate activation of CDK5 due to the proteolytic release of the activator fragment p25 from the membrane contributes to the formation of neurofibrillary tangles and chronic neurodegeneration. At 18 months of age 3xTg-AD mice were sacrificed after 1 year (long term) or 3 weeks (short term) of CDK5 knockdown. In long-term animals CDK5 knockdown prevented insoluble Tau formation in the hippocampi and prevented spatial memory impairment. In short-term animals, CDK5 knockdown showed reduction of CDK5, reversed Tau aggregation, and improved spatial memory compared to scrambled treated old 3xTg-AD mice. Neither long-term nor short-term CDK5 knock-down had an effect on old littermates. These findings further validate CDK5 as a target for Alzheimer’s disease both as a preventive measure and after the onset of symptoms.
Highlights
Alzheimer’s disease (AD) is the most common cause of dementia in people over 65 with about 24 million people affected worldwide (Reitz et al, 2011)
AD is characterized by abnormal folding and aggregation of β-amyloid protein as amyloid plaques and hyperphosphorylated Tau as neurofibrillary tangles (NFT)
LONG STANDING PREVENTION OF SPATIAL MEMORY IMPAIRMENT IN 3xTg-AD 1 YEAR AFTER Cyclin-dependent kinase 5 (CDK5) KNOCKDOWN Six-month-old 3xTg-AD mice were injected with either shCDK5miR or shSCRmiR in CA1 and were evaluated by Morris Water Maze (MWM) test 1 year post-injection
Summary
Alzheimer’s disease (AD) is the most common cause of dementia in people over 65 with about 24 million people affected worldwide (Reitz et al, 2011). AD is characterized by abnormal folding and aggregation of β-amyloid protein (βA) as amyloid plaques and hyperphosphorylated Tau as neurofibrillary tangles (NFT). These proteinopathies cause brain atrophy with marked cognitive impairment as the disease progresses (Querfurth and LaFerla, 2010). The phosphorylation/dephosphorylation rate of Tau by different kinases and phosphatases regulates MT function (Wang et al, 2007). An abnormal increase in Tau phosphorylation is associated with loss of its function, formation of paired helical filaments (PHF) and extracellular accumulation in NFT (Grundke-Iqbal et al, 1986; Kosik et al, 1986; Wang et al, 2007)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
