編者按：本期Science發(fā)表了一類非甾體抗炎藥抑制amyloid-ß peptide Aß42生成的機(jī)理。通過(guò)抑制Rho及其受體達(dá)到的,。揭示了這類藥物的作用本質(zhì),，為今后開發(fā)出更特異性的藥物打下基礎(chǔ),，也為AD病的治療帶來(lái)希望
Nonsteroidal Anti-Inflammatory Drugs Can Lower Amyloidogenic Aß42 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 M. Paul,* Binhui Ni
A subset of nonsteroidal anti-inflammatory drugs (NSAIDs) has been shown to preferentially reduce the secretion of the highly amyloidogenic, 42-residue amyloid-ß peptide Aß42. We found that Rho and its effector, Rho-associated kinase, preferentially regulated the amount of Aß42 produced in vitro and that only those NSAIDs effective as Rho inhibitors lowered Aß42. Administration of Y-27632, a selective Rock inhibitor, also preferentially lowered brain levels of Aß42 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 Aß42 through inhibition of Rho activity.
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