Pitavastatin decreases tau levels via the inactivation of Rho/ROCK

Tadanori Hamano, Shu Hui Yen, Tania D Gendron, Li wen Ko, Masaru Kuriyama

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Epidemiological studies have shown that long-term treatment with statins decreases the risk of developing Alzheimer's disease. Statins have pleiotropic effects by lowering the concentration of isoprenoid intermediates. Although several studies have shown that statins may reduce amyloid beta protein levels, there have been few reports on the interaction between statins and tau. We report here that pitavastatin reduces total and phosphorylated tau levels in a cellular model of tauopathy, and in primary neuronal cultures. The decrease caused by pitavastatin is reversed by the addition of mevalonate, or geranylgeranyl pyrophosphate. The maturation of small G proteins, including RhoA was disrupted by pitavastatin, as was the activity of glycogen synthase kinase 3β (GSK3β), a major tau kinase. Toxin A, inhibitor of glycosylation of small G proteins, and Rho kinase (ROCK) inhibitor decreased phosphorylated tau levels. Rho kinase inhibitor also inactivated glycogen synthase kinase 3β. Although the mechanisms responsible for the reduction in tau protein by pitavastatin require further examination, this report sheds light on possible therapeutic approaches to tauopathy.

Original languageEnglish (US)
Pages (from-to)2306-2320
Number of pages15
JournalNeurobiology of Aging
Volume33
Issue number10
DOIs
StatePublished - Oct 2012

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Hydroxymethylglutaryl-CoA Reductase Inhibitors
Tauopathies
Glycogen Synthase Kinase 3
rho-Associated Kinases
Monomeric GTP-Binding Proteins
tau Proteins
Amyloid beta-Peptides
Terpenes
Glycosylation
Protein Kinases
Epidemiologic Studies
Alzheimer Disease
Phosphotransferases
pitavastatin
Therapeutics

Keywords

  • Glycogen synthase kinase 3β
  • Neuronal cellular model
  • Pleiotrophic effects
  • Rho/ROCK
  • Small G protein
  • Statin
  • Tau

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Aging
  • Developmental Biology
  • Geriatrics and Gerontology

Cite this

Pitavastatin decreases tau levels via the inactivation of Rho/ROCK. / Hamano, Tadanori; Yen, Shu Hui; Gendron, Tania D; Ko, Li wen; Kuriyama, Masaru.

In: Neurobiology of Aging, Vol. 33, No. 10, 10.2012, p. 2306-2320.

Research output: Contribution to journalArticle

Hamano, Tadanori ; Yen, Shu Hui ; Gendron, Tania D ; Ko, Li wen ; Kuriyama, Masaru. / Pitavastatin decreases tau levels via the inactivation of Rho/ROCK. In: Neurobiology of Aging. 2012 ; Vol. 33, No. 10. pp. 2306-2320.
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