Reduction of Amyloid-ß Production without Inhibiting Secretase Activity by MS-275.
ACS Chem Neurosci
; 15(6): 1234-1241, 2024 03 20.
Article
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| MEDLINE
| ID: mdl-38416107
ABSTRACT
Brain amyloid-ß (Aß) governs the pathogenic process of Alzheimer's disease. Clinical trials to assess the disease-modifying effects of inhibitors or modulators of ß- and γ-secretases have not shown clinical benefit and can cause serious adverse events. Previously, we found that the interleukin-like epithelial-to-mesenchymal transition inducer (ILEI, also known as FAM3C) negatively regulates the Aß production through a decrease in Aß immediate precursor, without the inhibition of ß- and γ-secretase activity. Herein, we found that MS-275, a benzamide derivative that is known to inhibit histone deacetylases (HDACs), exhibits ILEI-like activity to reduce Aß production independent of HDAC inhibition. Chronic MS-275 treatment decreased Aß deposition in the cerebral cortex and hippocampus in an Alzheimer's disease mouse model. Overall, our results indicate that MS-275 is a potential therapeutic candidate for efficiently reducing brain Aß accumulation.
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Base de datos:
MEDLINE
Asunto principal:
Piridinas
/
Enfermedad de Alzheimer
Límite:
Animals
Idioma:
En
Revista:
ACS Chem Neurosci
Año:
2024
Tipo del documento:
Article
País de afiliación:
Japón