Nonsteroidal Anti-Inflammatpry Drugs Can Lower Amyloidogenic Aβ 42 by Inhibiting Rho

Yan Zhou, Yuan Su, Baolin Li, Feng Liu, John W. Ryder, Xin Wu, Patricia A. Gonzalez-DeWhitt, Valentina Gelfanova, John E. Hale, Patrick C. May, Steven H. Paul, Binhui Ni

Research output: Contribution to journalArticle

266 Scopus citations

Abstract

A subset of nonsteroidal anti-inflammatory drugs (NSAIDs) has been shown to preferentially reduce the secretion of the highly amyloidogenic, 42-residue amyloid-β peptide Aβ42. We found that Rho and its effector, Rho-associated kinase, preferentially regulated the amount of Aβ 42 produced in vitro and that only those NSAIDs effective as Rho inhibitors lowered Aβ42. Administration of Y-27632, a selective Rock inhibitor, also preferentially lowered brain levels of Aβ 42 in a transgenic mouse model of Alzheimer's disease. Thus, the Rho-Rock pathway may regulate amyloid precursor protein processing, and a subset of NSAIDs can reduce Aβ42 through inhibition of Rho activity.

Original languageEnglish
Pages (from-to)1215-1217
Number of pages3
JournalScience
Volume302
Issue number5648
DOIs
StatePublished - Nov 14 2003
Externally publishedYes

Fingerprint Dive into the research topics of 'Nonsteroidal Anti-Inflammatpry Drugs Can Lower Amyloidogenic Aβ <sub>42</sub> by Inhibiting Rho'. Together they form a unique fingerprint.

  • Cite this

    Zhou, Y., Su, Y., Li, B., Liu, F., Ryder, J. W., Wu, X., Gonzalez-DeWhitt, P. A., Gelfanova, V., Hale, J. E., May, P. C., Paul, S. H., & Ni, B. (2003). Nonsteroidal Anti-Inflammatpry Drugs Can Lower Amyloidogenic Aβ 42 by Inhibiting Rho. Science, 302(5648), 1215-1217. https://doi.org/10.1126/science.1090154