Targeting eNOS and beyond: Emerging heterogeneity of the role of endothelial Rho proteins in stroke protection

Naoki Sawada, James K. Liao

Research output: Contribution to journalReview articlepeer-review

28 Scopus citations


Currently available modalities for the treatment of acute ischemic stroke are aimed at preserving or augmenting cerebral blood flow. Experimental evidence suggests that statins, which show 25-30% reduction of stroke incidence in clinical trials, confer stroke protection by upregulation of eNOS and increasing cerebral blood flow. The upregulation of eNOS by statins is mediated by inhibition of small GTP-binding protein RhoA. Our recent study uncovered a unique role for a Rho-family member Rac1 in stroke protection. Rac1 in endothelium does not affect cerebral blood flow. Instead, inhibition of endothelial Rac1 leads to broad upregulation of the genes relevant to neurovascular protection. Intriguingly, inhibition of endothelial Rac1 enhances neuronal cell survival through endothelium-derived neurotrophic factors, including artemin. This review discusses the emerging therapeutic opportunities to target neurovascular signaling beyond the BBB, with special emphasis on the novel role of endothelial Rac1 in stroke protection.

Original languageEnglish (US)
Pages (from-to)1171-1186
Number of pages16
JournalExpert Review of Neurotherapeutics
Issue number8
StatePublished - 2009
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Clinical Neurology
  • Pharmacology (medical)


  • Blood-brain barrier
  • GTP-binding protein
  • Neurotrophic factors
  • Neurovascular unit
  • Rac1
  • Rho kinase
  • RhoA
  • Statins
  • Vascular endothelium
  • eNOS


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