Abstract
Alzheimer's disease is the most common dementia disease characterized by chronic progressive neurodegeneration. The incidence of Alzheimer's disease is on the rise as the population ages at an accelerating pace. According to epidemiological data, by 2050, the number of Alzheimer's patients in the United States will be three times higher than that in 2010, and a similar trend is occurring in China. To explore the effect and mechanism of let-7b by detecting the expression level of let-7b in Alzheimer's disease, fifty patients with Alzheimer's disease and thirty healthy controls were selected. The expression levels of let-7 families (let-7a, let-7b, let-7c, let-7d, let-7e, let-7f, let-7g, and let-7i) were detected by qPCR. Human neuroblastoma cell SK-N-SH were divided into control group (untreated), model group (treated with Aβ1-40), Aβ1-40+let-7b mimic group (treated with Aβ1-40 and transfected with let-7b mimic), and Aβ1-40+miR-NC group (treated with aβ1-40 and transfected with miR-NC). let-7b expression and cell survival rate were detected by qPCR and CCK-8, and the levels of caspase 3, LC3, beclin-1, PI3K, p-AKT, and p-mTOR were detected by Western blot. let-7b was significantly different between the case group and the control group (p < 0.001). CCK-8 showed a significant decrease in cell viability in Aβ1-40 treatment group compared with that in the control group (p < 0.01). Overexpression of let-7b significantly reduced the survival rate of the cells, and the expression of LC3II/LC3I and beclin-1 in the cells was significantly reduced by aβ1-40 treatment (p < 0.001). let-7b overexpression also inhibited autophagy via reducing the level of LC3II/LC3I and beclin-1 (p < 0.001). Aβ1-40 treatment and let-7b overexpression promoted apoptosis by increasing the expression of cleavage caspase 3. Western blot indicated that Aβ1-40 treatment and let-7b overexpression could increase the expression of PI3K, p-AKT, and p-mTOR. let-7b overexpression could inhibit autophagy and promote apoptosis in Alzheimer's cells by promoting PI3K/AKT/mTOR signaling pathway. PI3K/AKT/mTOR signaling pathway is involved in the imbalance between autophagy and apoptosis.
Highlights
Alzheimer’s disease is the most common dementia disease characterized by chronic progressive neurodegeneration [1].e incidence of Alzheimer’s disease is on the rise as the population ages at an accelerating pace
This study suggests that Aβ1-40 can induce apoptosis of SK-N-SH cells
Let-7b overexpression can increase the apoptosis of Aβ1-40 treated cells by damaging autophagy, in which process the PI3K/AKT/mammalian target of rapamycin (mTOR) signaling pathway is involved. let-7b can be used as a promising target and tool for Alzheimer’s disease treatment research, but the specific interaction target needs to be further studied
Summary
E incidence of Alzheimer’s disease is on the rise as the population ages at an accelerating pace. Alzheimer’s disease is a leading cause of disability and death, which brings a heavy burden to society and families [4]. E main pathological changes are neurofibrillary tangles, senile plaque deposition, and nerve cell death [5]. E key component of senile plaque has been proved to be β-amyloid (Aβ) [6, 7]. Deposition of Aβ1-40 is a key event in the development of pathogenic Aβ from diffusion to core plaque maturation and is the basis for the development of neurotoxic plaques in AD [8]. The role of autophagy in Alzheimer’s disease has attracted a wide range of attention.
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