Cdk5 in the adult non-demented brain.

André Fischer, Farahnaz Sananbenesi, Joachim Spiess, Jelena Radulovic

Research output: Contribution to journalReview articlepeer-review

14 Scopus citations

Abstract

Cyclin-dependent kinase 5 (Cdk5), a Ser/Thr kinase, regulates the phosphorylation of neuronal proteins and thereby influences neuronal morphology, migration and axon growth. Tightly coordinated interactions between Cdk5 and its activator proteins p35 and p39 are critical for the developmental processes of post-mitotic neurons as well as functioning of the adult CNS. Excessive up-regulation of Cdk5 activity leading to hyperphosphorylation of cytoskeletal proteins has been linked to neurodegenerative disorders, such as Alzheimer's disease (AD). On this basis it was proposed that Cdk5 might be a promising drug target. The physiologic role of Cdk5 in the adult CNS has been addressed recently. It was demonstrated that Cdk5 is involved in striatal and hippocampal neuronal plasticity and long-term behavioral changes associated with these processes. On the basis of the newly identified role of Cdk5 in synaptic plasticity, learning and memory the view that Cdk5 represents a good drug target in AD accompanied by cognitive dysfunctions may have to be revisited. Alternatively, targeting the mechanisms up-stream of Cdk5 leading to deregulation of Cdk5 activity, such as proteolytic cleavage of its activating subunits may prove to be more beneficial as a therapeutical approach.

Original languageEnglish (US)
Pages (from-to)375-381
Number of pages7
JournalCNS and Neurological Disorders - Drug Targets
Volume2
Issue number6
DOIs
StatePublished - Dec 2003
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)
  • Pharmacology

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