The BACE1-Specific DNA Aptamer A1 Rescues Amyloid-β Pathology and Behavioral Deficits in a Mouse Model of Alzheimer's Disease
| Autor: | Yong-Hua Peng, Yanling Liang, Xingmei Zhang, Shuji Li, Zhi-Man Liang, Yue Chen, Hong-Jie Luo, Ying-Hong Tian, Li-Li Long, Yusheng Shi, Ya-Jun Chen |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Aptamer Mice Transgenic Cleavage (embryo) Biochemistry Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Western blot Alzheimer Disease mental disorders Drug Discovery Genetics Amyloid precursor protein medicine Animals Aspartic Acid Endopeptidases Humans Senile plaques Molecular Biology chemistry.chemical_classification Amyloid beta-Peptides biology medicine.diagnostic_test Chemistry Brain Genetic Therapy Aptamers Nucleotide Molecular biology Disease Models Animal Infusions Intraventricular 030104 developmental biology Enzyme 030220 oncology & carcinogenesis biology.protein Molecular Medicine Amyloid Precursor Protein Secretases DNA Systematic evolution of ligands by exponential enrichment |
| Zdroj: | Nucleic Acid Therapeutics. 29:359-366 |
| ISSN: | 2159-3345 2159-3337 |
| Popis: | Amyloid-β (Aβ) 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 β-site APP-cleaving enzyme 1 (BACE1) and γ-secretase produces Aβ. 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 β (sAPPβ) expression significantly decreased in the A1-treated mice. Moreover, aptamer A1 reduced the content of Aβ42 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. |
| Databáze: | OpenAIRE |
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