MicroRNA-16 targets amyloid precursor protein to potentially modulate Alzheimer's-associated pathogenesis in SAMP8 mice.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder mainly characterized by amyloid-beta (Aβ) deposition and neurofibrillary tangles (NFTs). The abnormal enrichment of amyloid protein precursor (APP) leads to a high risk of AD. One of the plausible age-associated AD animal models, senescence-accelerated mouse prone 8 (SAMP8), have age-related learning and memory deficits. We found APP protein significantly increased in the hippocampus of aged SAMP8 mice. The 20 to 25 nucleotide (nt) tiny regulators, known as micro ribonucleic acids (miRNAs), have been found to play crucial roles in neurodegenerative diseases. Here, we examined the post-transcriptional regulation mechanism of APP mediated by micro ribonucleic acids and found that miR-16 was one of the post-transcriptional regulators of APP in SAMP8 mice. Overexpression of miR-16, both in vitro and in vivo, led to reduced APP protein expression. Furthermore, miR-16 and APP displayed complementary expression patterns in SAMP8 mice and BALb/c mice embryos. Taken together, these findings demonstrate that APP is a target of miR-16 and the abnormally low expression of miR-16 could potentially lead to APP protein accumulation in AD mice.
Liu
Wei
W
The National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
Liu
Chang
C
Zhu
Jingxi
J
Shu
Pengcheng
P
Yin
Bin
B
Gong
Yanhua
Y
Qiang
Boqin
B
Yuan
Jiangang
J
Peng
Xiaozhong
X
D019588:Aging, Premature / Q000235:genetics* / Q000378:metabolism; D000544:Alzheimer Disease / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008818:Mice, Neurologic Mutants; D035683:MicroRNAs / Q000235:genetics*; D041681:NIH 3T3 Cells; D009447:Neuroblastoma / Q000235:genetics
D016564:Amyloid beta-Protein Precursor; D035683:MicroRNAs; C522604:Mirn16 microRNA, mouse