阿爾茲海默症（AD）是常見一種神經退行性變，可能用老年痴呆來描述這種疾病更容易被理解，AD是常見的一種老年痴呆的類型，很多名人如拳王阿里，美國總統里根等。不僅嚴重影響患者的生活質量，而且增加患者家屬的經濟負擔。但其發病機制及治療方法到目前為止尚不清楚。
對其分子機制的研究有助對其發病機制的更深入瞭解，也有助於發現新的治療策略。
摘要翻譯
鑑定LncRNA-miRNA-mRNA網絡研究阿爾茨海默病的發病機制和治療策略
鑑定LncRNA-miRNA-mRNA網絡研究阿爾茨海默病的發病機制和治療策略。阿爾茨海默病(AD)是導致痴呆症的最常見原因，它會導致老年腦的神經元損傷和認知功能惡化。有證據表明非編碼RNA參與了AD相關的病理生理學機制。
AD和LncRNA相關的競爭內源RNA(CERNA)網絡之間的潛在聯繫已經被揭示。然而，至今仍沒有全基因組研究確定與AD相關的LncRNA-CERNA對。
為此，我們採用深層RNA測序的方法，系統地研究了AD模型小鼠(APP/PS1)腦內與LncRNA相關的CERNA網絡。
我們的結果分別鑑定了48789和3025個顯著失調的LncRNA、miRNAs和mRNAs，並在APP/PS1腦中構建了迄今為止最全面的與LncRNA相關的CERNA網絡。GO分析顯示，已識別的網絡從不同的來源，如突觸和樹突，參與調控AD的發展。經過嚴格篩選，該AD小鼠模型中與lncRNA相關的CERNA網絡被發現主要參與突觸可塑性和記憶(AKAP5)和調節澱粉樣蛋白(Aβ)誘導的神經炎症(KLF4)。
這項研究首次系統地剖析了APP/PS1小鼠大腦中與LncRNA相關的CERNA圖譜。鑑別出的與LncRNA相關的CERNA網絡有助於AD診斷和提出未來治療的新策略。關鍵詞：APP/PS1小鼠；阿爾茨海默病；RNA測序；CERNA網絡；LncRNA。
原文摘要
Identifying lncRNA-miRNA-mRNA Networks to Investigate Alzheimer's Disease Pathogenesis and Therapy Strategy
Alzheimer's disease (AD), the most common cause of dementia, leads to neuronal damage and deterioration of cognitive functions in aging brains. There is evidence suggesting the participation of noncoding RNAs in AD-associated pathophysiology. A potential linkage between AD and lncRNA-associated competing endogenous RNA (ceRNA) networks has been revealed. Nevertheless, there are still no genome-wide studies which have identified the lncRNA-associated ceRNA pairs involved in AD. For this reason, deep RNA-sequencing was performed to systematically investigate lncRNA-associated ceRNA mechanisms in AD model mice (APP/PS1) brains. Our results identified 487, 89, and 3,025 significantly dysregulated lncRNAs, miRNAs, and mRNAs, respectively, and the most comprehensive lncRNA-associated ceRNA networks to date are constructed in the APP/PS1 brain. GO analysis revealed the involvement of the identified networks in regulating AD development from distinct origins, such as synapses and dendrites. Following rigorous selection, the lncRNA-associated ceRNA networks in this AD mouse model were found to be mainly involved in synaptic plasticity as well as memory (Akap5) and regulation of amyloid-β (Aβ)-induced neuroinflammation (Klf4). This study presents the first systematic dissection of lncRNA-associated ceRNA profiles in the APP/PS1 mouse brain. The identified lncRNA-associated ceRNA networks could provide insights that facilitate AD diagnosis and future treatment strategies.
Keywords: APP/PS1 mouse; Alzheimer’s disease (AD); RNA-sequencing; ceRNA n
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