TY - JOUR
T1 - Nonsteroidal Anti-Inflammatpry Drugs Can Lower Amyloidogenic Aβ 42 by Inhibiting Rho
AU - Zhou, Yan
AU - Su, Yuan
AU - Li, Baolin
AU - Liu, Feng
AU - Ryder, John W.
AU - Wu, Xin
AU - Gonzalez-DeWhitt, Patricia A.
AU - Gelfanova, Valentina
AU - Hale, John E.
AU - May, Patrick C.
AU - Paul, Steven H.
AU - Ni, Binhui
PY - 2003/11/14
Y1 - 2003/11/14
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0242414463&partnerID=8YFLogxK
U2 - 10.1126/science.1090154
DO - 10.1126/science.1090154
M3 - Article
C2 - 14615541
AN - SCOPUS:0242414463
SN - 0036-8075
VL - 302
SP - 1215
EP - 1217
JO - Science
JF - Science
IS - 5648
ER -