• Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

Hyperphosphorylated tau and neurofilament and cytoskeletal disruptions in mice overexpressing human p25, an activator of cdk5.

Hyperphosphorylation of microtubule-associated proteins such as tau and neurofilament may underlie the cytoskeletal abnormalities and neuronal death seen in several neurodegenerative diseases including Alzheimer's disease. One potential mechanism of microtubule-associated protein hyperphosphorylation is augmented activity of protein kinases known to associate with microtubules, such as cdk5 or GSK3beta. Here we show that tau and neurofilament are hyperphosphorylated in transgenic mice that overexpress human p25, an activator of cdk5. The p25 transgenic mice display silver-positive neurons using the Bielschowsky stain. Disturbances in neuronal cytoskeletal organization are apparent at the ultrastructural level. These changes are localized predominantly to the amygdala, thalamus/hypothalamus, and cortex. The p25 transgenic mice display increased spontaneous locomotor activity and differences from control in the elevated plus-maze test. The overexpression of an activator of cdk5 in transgenic mice results in increased cdk5 activity that is sufficient to produce hyperphosphorylation of tau and neurofilament as well as cytoskeletal disruptions reminiscent of Alzheimer's disease and other neurodegenerative diseases.

Pubmed ID: 10706614

Authors

  • Ahlijanian MK
  • Barrezueta NX
  • Williams RD
  • Jakowski A
  • Kowsz KP
  • McCarthy S
  • Coskran T
  • Carlo A
  • Seymour PA
  • Burkhardt JE
  • Nelson RB
  • McNeish JD

Journal

Proceedings of the National Academy of Sciences of the United States of America

Publication Data

March 14, 2000

Associated Grants

None

Mesh Terms

  • Age Factors
  • Alzheimer Disease
  • Animals
  • Brain
  • Cyclin-Dependent Kinase 5
  • Cyclin-Dependent Kinases
  • Cytoskeleton
  • Epitopes
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Mice
  • Mice, Transgenic
  • Microscopy, Electron
  • Nerve Tissue Proteins
  • Neurofilament Proteins
  • Phosphorylation
  • Sex Factors
  • Silver Staining
  • tau Proteins