The endocannabinoid system offers a target for Alzheimer's disease treatment through inhibition of fatty acid amide hydrolase (FAAH)

被引：0
|
作者：
de Ceballos, Maria L. [1 ]
机构：
[1] CSIC, Cajal Inst, Dept Translat Neurosci, Ave Doctor Arce 37, Madrid 28002, Spain
来源：
FEBS JOURNAL | 2025年
关键词：
Alzheimer's disease; amyloidogenic mouse models; APP/PS1; fatty acid amide hydrolase; N-arachidonoylethanolamine; Tg2576; beta-site amyloid precursor protein-cleaving enzyme 1; CANNABINOID CB2 RECEPTORS;
D O I：
10.1111/febs.70082
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Oddi et al. report the effects of chronic treatment via intranasal delivery with URB597, a fatty acid amide hydrolase (FAAH) inhibitor, on an Alzheimer's disease (AD) transgenic mouse model. They found that prolonged treatment with URB597 reduced the learning and memory deficits of these mice. Mechanistically, the inhibitor modified several genes related to amyloidosis and inflammatory responses or anandamide signaling. FAAH inhibition induced a decrease in the accumulation, synthesis, and release of beta-Amyloid, along with diminished expression of beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1), and this change may be associated with epigenetic changes induced by the drug. In summary, prolonged treatment with URB597 impinges on different aspects of AD pathophysiology, suggesting its therapeutic relevance in treating AD.
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页数：4
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