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Series GSE62240 Query DataSets for GSE62240
Status Public on Nov 27, 2015
Title A novel approach to Alzheimer’s Disease treatment: HDACs & PDE5 inhibition
Organism Mus musculus
Experiment type Expression profiling by array
Summary Considering the numerous complex and different pathological mechanisms involved in Alzheimer´s disease (AD) progression, treatments targeting a single cause may lead to limited benefits. The goal of this study was the identification of a novel mode of action for this unmet need. Pharmacological tool compounds: suberoylanilide hydroxamic acid (SAHA) and tadalafil, targeting histone deacetylases (HDAC) and phosphodiesterase 5 (PDE5) respectively, were utilized simultaneously for in-vitro and in-vivo Proof-of-Concept (PoC). A synergistic effect was observed in the amelioration of AD signs using the combination therapy in Tg2576 mice. Finally, a therapeutic agent, CM-414, inhibiting simultaneously HDAC2/6 and PDE5 was generated and tested in Tg2576 mice. CM-414 reversed cognitive impairment, reduced amyloid and tau pathology, and rescued dendritic spine density loss in the hippocampus in AD mice. Importantly, the effect obtained was present after a 4-weeks wash-out period.
 
Overall design Comparisson of global gene expression profiling in mice hippocampi between diferent treatments
 
Contributor(s) García-Osta A, Cuadrado M, Oyarzábal J, Segura V
Citation(s) 26457123, 27550730
Submission date Oct 10, 2014
Last update date Mar 11, 2020
Contact name Victor Segura
E-mail(s) vsegura@unav.es
Organization name FIMA
Department Unit of Proteomics, Genomics and Bioinformatics
Street address Avda. Pío XII, 55
City Pamplona
State/province Navarra
ZIP/Postal code 31008
Country Spain
 
Platforms (1)
GPL16570 [MoGene-2_0-st] Affymetrix Mouse Gene 2.0 ST Array [transcript (gene) version]
Samples (24)
GSM1523465 Hippocampus vehicle. Biological replica 1
GSM1523466 Hippocampus vehicle. Biological replica 2
GSM1523467 Hippocampus vehicle. Biological replica 3
Relations
BioProject PRJNA263566

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE62240_RAW.tar 219.2 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table
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