Reduction of Blood Amyloid-ß Oligomers in Alzheimer's Disease Transgenic Mice by c-Abl Kinase Inhibition.
J Alzheimers Dis
; 54(3): 1193-1205, 2016 10 04.
Article
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| MEDLINE
| ID: mdl-27567806
ABSTRACT
One of the pathological hallmarks of Alzheimer's disease (AD) is the presence of amyloid plaques, which are deposits of misfolded and aggregated amyloid-beta peptide (Aß). The role of the c-Abl tyrosine kinase in Aß-mediated neurodegeneration has been previously reported. Here, we investigated the therapeutic potential of inhibiting c-Abl using imatinib. We developed a novel method, based on a technique used to detect prions (PMCA), to measure minute amounts of misfolded-Aß in the blood of AD transgenic mice. We found that imatinib reduces Aß-oligomers in plasma, which correlates with a reduction of AD brain features such as plaques and oligomers accumulation, neuroinflammation, and cognitive deficits. Cells exposed to imatinib and c-Abl KO mice display decreased levels of ß-CTF fragments, suggesting that an altered processing of the amyloid-beta protein precursor is the most probable mechanism behind imatinib effects. Our findings support the role of c-Abl in Aß accumulation and AD, and propose AD-PMCA as a new tool to evaluate AD progression and screening for drug candidates.
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Bases de datos:
MEDLINE
Asunto principal:
Péptidos beta-Amiloides
/
Proteínas Proto-Oncogénicas c-abl
/
Inhibidores de Proteínas Quinasas
/
Enfermedad de Alzheimer
Límite:
Animals
Idioma:
En
Revista:
J Alzheimers Dis
Asunto de la revista:
GERIATRIA
/
NEUROLOGIA
Año:
2016
Tipo del documento:
Article
País de afiliación:
Chile