期刊
NUCLEIC ACID THERAPEUTICS
卷 29, 期 6, 页码 359-366出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/nat.2019.0812
关键词
BACE1 inhibitor; Alzheimer's disease; amyloid plaques; aptamer; SELEX
资金
- National Natural Science Foundation of China [81471388, 81771484, 81871418]
- Natural Science Foundation of Guangdong Province, China [2018A030313835]
- Program for Changjiang Scholars and Innovative Research Team in University [IRT_16R37]
- Guangzhou Science and Technology Project [201707020027]
Amyloid-beta (A beta) plaque deposits in the brain are considered to be one of the main pathological markers of Alzheimer's disease (AD). The sequential proteolytic cleavage of amyloid precursor protein (APP) by the aspartyl proteases beta-site APP-cleaving enzyme 1 (BACE1) and gamma-secretase produces A beta. Therefore, BACE1 inhibition is a very attractive target for the treatment of AD. Our previous work identified a DNA aptamer named A1 that can bind to BACE1 with high affinity and specificity and exhibits a distinct inhibitory effect on BACE1 activity in an AD cell model. The purpose of this research was to test the effect of aptamer A1 in Tg6799 mice. Four-month-old Tg6799 mice were randomly divided into two groups and treated with aptamer A1 and ineffective aptamer A1scr, respectively, by intracerebroventricular injection. Subsequent behavioral experiments showed that treatment with the aptamer A1 improved the cognitive abilities of the AD mice. Western blot indicated that BACE1 and soluble amyloid precursor protein beta (sAPP beta) expression significantly decreased in the A1-treated mice. Moreover, aptamer A1 reduced the content of A beta(42) and the number and density of senile plaques in AD mice. Therefore, our results indicate that aptamer A1 is a novel specific and potent BACE1 inhibitor and is a promising potential target for the treatment of AD.
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