Linked Life Data

15975083

Source:http://linkedlifedata.com/resource/pubmed/id/15975083

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2005-6-24
pubmed:abstractText
Based on a growing literature, cyclin-dependent kinase 5 (Cdk5) has been implicated in the pathological processes that contribute to neurodegeneration in Alzheimer's disease (AD). Cdk5 is ubiquitously expressed, but its activity is largely localized to post-mitotic neurons due to neuron-specific expression of its activators p35 and p39. Sufficient Cdk5 activity is critical to normal central nervous system development, as in its absence, neuronal migration and axonal path finding are deranged. Conversely, excessive and mislocalized Cdk5 activity appears to be detrimental to neuronal function. In fact, the pathological hallmarks of AD, beta-amyloid aggregates and neurofibrillary tangles, have been linked to Cdk5-mediated neuronal death. In this model, beta-amyloid is the toxic stimulus that disrupts intracellular calcium homeostasis, leading to activation of calpains, a family of calcium-dependent proteases. Calpain-mediated cleavage of p35, yields a truncated p25 fragment that possesses a longer half-life, lacks the necessary sequence targeting it to membranes, but retains the capacity to activate Cdk5. The resulting excessive and mislocalized Cdk5 activity targets tau as a substrate for hyperphosphorylation, which is a prerequisite of paired helical filament (PHF) formation. A number of recent reports, utilizing diverse methods, lend further support to this model of AD neurodegeneration, and several strategies for combating Cdk5 dysregulation have even been devised. However, the study of Cdk5 in AD is not without controversy, and questions remain regarding its role in the pathology. Herein, the most recent findings regarding this model are reviewed.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1567-2050
pubmed:author
pubmed:issnType
Print
pubmed:volume
1
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
33-8
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Recent evidence regarding a role for Cdk5 dysregulation in Alzheimer's disease.
pubmed:affiliation
Department of Pharmacology, SUNY Upstate Medical University, Syracuse, NY 13210, USA. monacoe@upstate.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Review, Research Support, N.I.H., Extramural