NcRNAs: A synergistically antiapoptosis therapeutic tool in Alzheimer's disease

Abstract

Aims: The aim of this review is to systematically summarize and analyze the noncoding RNAs (ncRNAs), especially microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), in the cell apoptosis among Alzheimer's disease (AD) in recent years to demonstrate their value in the diagnosis and treatment of AD.

Methods: We systematically summarized in vitro and in vivo studies focusing on the ncRNAs in the regulation of cell apoptosis among AD in PubMed, ScienceDirect, and Google Scholar.

Results: We discover three patterns of ncRNAs (including 'miRNA-mRNA', 'lncRNA-miRNA-mRNA', and 'circRNA-miRNA-mRNA') form the ncRNA-based regulatory networks in regulating cell apoptosis in AD.

Conclusions: This review provides a future diagnosis and treatment strategy for AD patients based on ncRNAs.

Keywords: AD; NcRNAs; cell apoptosis; regulatory network.

FIGURE 1

Apoptosis is triggered by the intrinsic and extrinsic pathways. The intrinsic pathway is activated by BAK and BAX. BAK/BAX oligomers form pores, leading to the release of Cytochrome c into the cytosol. Activation of BAK/BAX is promoted by BID or inhibited by BCL‐2/BCL‐XL/BCL‐W. Cytochrome c binds to Apaf‐1, which recruits Pro‐Caspase‐9, forming the apoptosome. In the apoptosome, Pro‐Caspase‐9 is activated by autoproteolytic cleavage, initiating the caspase‐processing cascade. The extrinsic pathway is activated by engagement of membrane receptors. These proteins induce DISC involving TRADD, FADD, Caspase‐8, and Caspase‐10. Initiator Caspase‐8/10 activation is negatively regulated by c‐FLIP. Once active, executioner caspases (Caspase‐3/6/7) bring about apoptosis.

FIGURE 2

The potential synergistically antiapoptosis ncRNA‐based regulatory networks exist in AD. (A) Based on miR‐107, the network is constructed in regulating cell apoptosis in AD and the simple antiapoptotic strategy is proposed. (B) Based on BACE1, the network is constructed in regulating cell apoptosis in AD and the simple antiapoptotic strategy is proposed. Red arrows (‘’ and ‘’) present for upregulation and downregulation, respectively.

FIGURE 3

The potential synergistically ncRNA‐based apoptosis regulatory mechanism exists in AD. First, three independent regulatory axes in left, ‘miRNA‐mRNA’, ‘lncRNA‐miRNA‐mRNA’, and ‘circRNA‐miRNA‐mRNA’, regulate cell apoptosis in AD. Then, intertwined ncRNA‐based regulatory network in right regulates cell apoptosis in AD.