RT Journal Article
T1 Mifepristone alters amyloid precursor protein processing to preclude amyloid beta and also reduces tau pathology
A1 Baglietto-Vargas, David
A1 Medeiros, Rodrigo
A1 Martinez-Coria, Hilda
A1 LaFerla, Frank M.
A1 Green, Kim N
K1 Alzheimer, Enfermedad de
AB BackgroundIncreased circulating glucocorticoids are features of both aging and Alzheimer’s disease (AD), and increased glucocorticoids accelerate the accumulation of AD pathologies. Here, we analyzed the effects of the glucocorticoid receptor antagonist mifepristone (RU486) in the 3xTg-AD mouse model at an age where hippocampal damage leads to high circulating corticosterone levels.MethodsThe effects of mifepristone were investigated in 3xTg-AD mice using a combination of biochemical, histological, and behavior analyses.ResultsMifepristone treatment rescues the pathologically induced cognitive impairments and markedly reduces amyloid beta (Aβ)-load and levels, as well as tau pathologies. Analysis of amyloid precursor protein (APP) processing revealed concomitant decreases in both APP C-terminal fragments C99 and C83 and the appearance of a larger 17-kDa C-terminal fragment. Hence, mifepristone induces a novel C-terminal cleavage of APP that prevents it being cleaved by α- or β-secretase, thereby precluding Aβ generation in the central nervous system; this cleavage and the production of the 17-kDa APP fragment was generated by a calcium-dependent cysteine protease. In addition, mifepristone treatment also reduced the phosphorylation and accumulation of tau, concomitant with reductions in p25. Notably, deficits in cyclic-AMP response element-binding protein signaling were restored with the treatment.
PB Elsevier
YR 2013
FD 2013-09-01
LK https://hdl.handle.net/10630/36413
UL https://hdl.handle.net/10630/36413
LA eng
NO Baglietto-Vargas D, Medeiros R, Martinez-Coria H, LaFerla FM, Green KN. Mifepristone alters amyloid precursor protein processing to preclude amyloid beta and also reduces tau pathology. Biol Psychiatry. 2013 Sep 1;74(5):357-66. doi: 10.1016/j.biopsych.2012.12.003. Epub 2013 Jan 8. PMID: 23312564; PMCID: PMC3633722.
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 20 ene 2026