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 journalArticlepeer-review

305 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

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