Activation of melatonin receptor 1 by CRISPR-Cas9 activator ameliorates cognitive deficits in an Alzheimer's disease mouse model

被引:17
作者
Park, Hanseul [1 ]
Kim, Jongpil [1 ]
机构
[1] Dongguk Univ, Dept Chem, Lab Stem Cells & Cell Reprogramming, Seoul 100715, South Korea
基金
新加坡国家研究基金会;
关键词
Alzheimer's disease; Cas9; activator; melatonin receptor; Mt1; TRAUMATIC BRAIN-INJURY; OXIDATIVE STRESS; SUPRACHIASMATIC NUCLEUS; TRANSCRIPTIONAL ACTIVATION; CEREBROSPINAL-FLUID; MEMORY IMPAIRMENT; MT1; RECEPTOR; DRUG; MECHANISMS; REDUCTION;
D O I
10.1111/jpi.12787
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the presence of neurotoxic beta-amyloid (A beta) in the brain. Melatonin receptors have been reported to associate with aging and AD, and their expression decreased with the progression of AD. As an alternative to AD treatment, overexpression of melatonin receptors may lead to melatonin-like effects to treat alleviate the symptoms of AD. Here, we successfully activated the type 1 melatonin receptor (Mt1) in vivo brain using a Cas9 activator as a novel AD therapeutic strategy. The Cas9 activator efficiently activated the endogenous Mt1 gene in the brain. Activation of Mt1 via Cas9 activators modulated anti-amyloidogenic and anti-inflammatory roles in 5xFAD AD mice brain. Moreover, activation of Mt1 with the CRISPR/Cas9 activator improved cognitive deficits in an AD model. These results demonstrated the therapeutic potential of melatonin receptor activation via CRISPR/Cas9 activator for AD.
引用
收藏
页数:14
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