Improved cognitive impairments by silencing DMP1 via enhancing the proliferation of neural progenitor cell in Alzheimer-like mice.
Improved cognitive impairments by silencing DMP1 via enhancing the proliferation of neural progenitor cell in Alzheimer-like mice.
复制标题
通过增强阿尔茨海默样小鼠神经祖细胞的增殖来沉默 DMP1，从而改善认知障碍
作者：
阿尔茨海默病（AD）是与年龄相关的进行性神经功能障碍。目前有限的临床疗效表明迫切需要新的治疗策略。先前的转录组学分析表明，DMP1在AD模型动物中的表达水平升高，而它可以在几种细胞系中诱导细胞周期阻滞。然而，DMP1诱导的神经祖细胞细胞周期阻滞是否影响阿尔茨海默样小鼠的认知功能仍不清楚。我们研究的目的是探讨这个问题。通过对ADNI数据库的临床基因组分析，我们发现DMP1与认知功能相关。通过体外沉默和过表达DMP1，揭示了DMP1对神经祖细胞（NPC）增殖的负面作用。此外，通过降低P53和P21水平，沉默DMP1可以增加NPCs的数量并改善阿尔茨海默样小鼠的认知功能，这表明DMP1诱导的细胞周期阻滞可能影响认知功能。神经祖细胞（NPC）在治疗阿尔茨海默病（AD）的内源性再生神经元中发挥了重要作用。临床基因组学数据和AD动物模型实验表明，DMP1与认知功能和鼻咽癌增殖有关。沉默DMP1可通过增加新生儿NPC和神经元来改善AD动物模型的认知功能。数据显示，DMP1通过刺激鼻咽癌增殖，在AD治疗中具有潜在作用。
Alzheimer's disease (AD) is age‐related progressive neurological dysfunction. Limited clinical benefits for current treatments indicate an urgent need for novel therapeutic strategies. Previous transcriptomic analysis showed that DMP1 expression level was increased in AD model animals whereas it can induce cell‐cycle arrest in several cell lines. However, whether the cell‐cycle arrest of neural progenitor cell induced by DMP1 affects cognitive function in Alzheimer‐like mice still remains unknown. The objective of our study is to explore the issue. We found that DMP1 is correlated with cognitive function based on the clinical genomic analysis of ADNI database. The negative role of DMP1 on neural progenitor cell (NPC) proliferation was revealed by silencing and overexpressing DMP1 in vitro. Furthermore, silencing DMP1 could increase the number of NPCs and improve cognitive function in Alzheimer‐like mice, through decreasing P53 and P21 levels, which suggested that DMP1‐induced cell‐cycle arrest could influence cognitive function. Neural progenitor cells (NPC) emerged their roles in endogenous regenerating neurons for Alzheimer's disease (AD) treatments. Clinical genomics data and AD animal model experiments suggested that DMP1 was related to cognitive function and NPC proliferation. Silencing DMP1 could improve cognitive function through increase newborn NPC and neurons in AD animal model. Data demonstrated the potential role of DMP1 for AD treatment by stimulating NPC proliferation.
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影响因子：
11.2
作者：
Frazier DP;Kendig RD;Kai F;Maglic D;Sugiyama T;Morgan RL;Fry EA;Lagedrost SJ;Sui G;Inoue K
通讯作者：
Inoue K
影响因子：
8
作者：
Maglic, D.;Zhu, S.;Fry, E. A.;Taneja, P.;Kai, F.;Kendig, R. D.;Sugiyama, T.;Miller, L. D.;Willingham, M. C.;Inoue, K.
通讯作者：
Inoue, K.
影响因子：
5.9
作者：
Huang S;Mao J;Ding K;Zhou Y;Zeng X;Yang W;Wang P;Zhao C;Yao J;Xia P;Pei G
通讯作者：
Pei G
影响因子：
3.7
作者：
Bekinschtein, Pedro;Katche, Cynthia;Medina, Jorge H.
通讯作者：
Medina, Jorge H.
影响因子：
6
作者：
Cha MY;Kwon YW;Ahn HS;Jeong H;Lee YY;Moon M;Baik SH;Kim DK;Song H;Yi EC;Hwang D;Kim HS;Mook-Jung I
通讯作者：
Mook-Jung I