MicroRNA-16 targets amyloid precursor protein to potentially modulate Alzheimer's-associated pathogenesis in SAMP8 mice

• DOI: 10.1016/j.neurobiolaging.2010.04.034
• Publication Date: 2010-07-09T08:18:55Z
• Authors: Wei Liu; Chang Liu; Jingxi Zhu; Pengcheng Shu; Bin Yin; Yanhua Gong; Boqin Qiang; Jiangang Yuan; Xiaozhong Peng
• Keywords: Mice, Inbred BALB C; 0303 health sciences; Aging, Premature; Amyloid beta-Protein Precursor; Disease Models, Animal; Mice; Mice, Neurologic Mutants; MicroRNAs; Neuroblastoma; 03 medical and health sciences; HEK293 Cells; Alzheimer Disease; Cell Line, Tumor; NIH 3T3 Cells; Animals; Humans

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.