Is there a role of the cyclin-dependent kinase 5 activator p25 in Alzheimer's disease?

Karl Peter Giese, Laurence Ris, Florian Plattner

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Sporadic Alzheimer's disease is the leading cause of dementia, but the underlying molecular processes are still unknown. Several studies have observed an accumulation of the protein fragment p25 in sporadic Alzheimer's disease brain. p25 derives from proteolysis of p35, and overactivates the tau kinase cyclin-dependent kinase 5. Transgenic mice expressing high levels of p25 exhibit hyperphosphorylation of tau as seen in Alzheimer's disease, and neurodegeneration. In contrast, low-level p25 expression, less than half of endogenous p35 expression, has a sex-specific effect on hippocampal synaptic plasticity and improves spatial learning in female but not in male mice. Therefore, p25 formation may initially be a compensatory response for early learning deficits in Alzheimer's disease, but continued formation could contribute to detrimental changes in Alzheimer's disease.

Original languageEnglish (US)
Pages (from-to)1725-1730
Number of pages6
JournalNeuroReport
Volume16
Issue number16
DOIs
StatePublished - Nov 7 2005

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Cyclin-Dependent Kinase 5
Alzheimer Disease
Neuronal Plasticity
Transgenic Mice
Proteolysis
Dementia
Phosphotransferases
Learning
Brain
Proteins

Keywords

  • Cyclin-dependent kinase 5
  • Memory
  • Neurodegeneration
  • Sex difference
  • Synaptic plasticity
  • Transgenic mice

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Is there a role of the cyclin-dependent kinase 5 activator p25 in Alzheimer's disease? / Giese, Karl Peter; Ris, Laurence; Plattner, Florian.

In: NeuroReport, Vol. 16, No. 16, 07.11.2005, p. 1725-1730.

Research output: Contribution to journalArticle

Giese, Karl Peter ; Ris, Laurence ; Plattner, Florian. / Is there a role of the cyclin-dependent kinase 5 activator p25 in Alzheimer's disease?. In: NeuroReport. 2005 ; Vol. 16, No. 16. pp. 1725-1730.
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