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Review
. 2024 Sep 10;14(1):367.
doi: 10.1038/s41398-024-03075-8.

MicroRNAs: pioneering regulators in Alzheimer's disease pathogenesis, diagnosis, and therapy

Yao-Bo Li  1 , Qiang Fu  2 , Mei Guo  3 , Yang Du  2 , Yuewen Chen  4   5 , Yong Cheng  6   7   8
Affiliations
Review

MicroRNAs: pioneering regulators in Alzheimer's disease pathogenesis, diagnosis, and therapy

Yao-Bo Li et al. Transl Psychiatry. .

Abstract

This article delves into Alzheimer's disease (AD), a prevalent neurodegenerative condition primarily affecting the elderly. It is characterized by progressive memory and cognitive impairments, severely disrupting daily life. Recent research highlights the potential involvement of microRNAs in the pathogenesis of AD. MicroRNAs (MiRNAs), short non-coding RNAs comprising 20-24 nucleotides, significantly influence gene regulation by hindering translation or promoting degradation of target genes. This review explores the role of specific miRNAs in AD progression, focusing on their impact on β-amyloid (Aβ) peptide accumulation, intracellular aggregation of hyperphosphorylated tau proteins, mitochondrial dysfunction, neuroinflammation, oxidative stress, and the expression of the APOE4 gene. Our insights contribute to understanding AD's pathology, offering new avenues for identifying diagnostic markers and developing novel therapeutic targets.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. MiRNAs biogenesis.
The microRNA (miRNA) biosynthesis pathway is categorized into classical and non-classical. (1) In the classical pathway, miRNA genes are transcribed to generate primary miRNAs (pri-miRNAs), which are processed by Drosha and DGCR8 to form precursor miRNAs (pre-miRNAs), and then transferred to the cytoplasm where Dicer generates double-stranded miRNAs, which ultimately bind to RISC to regulate the translation of target mRNAs; (2) the non-classical pathway directly generates double-stranded miRNA. [miRNA microRNA, Pri-miRNA primary microRNA), Pre-miRNA precursor microRNA, RISC RNA-induced silencing complex, mRNA (messenger RNA, ORF open reading frame, Ago Argonaute, DGCR8 DiGeorge Syndrome Critical Region 8, Dicer Dicer enzyme].
Fig. 2
Fig. 2. Summary of miRNAs and the targets in AD.
Specific microRNAs play key roles in the development of Alzheimer's disease (AD), regulating Aβ deposition, Tau hyperphosphorylation, synaptic dysfunction, neuroinflammation, oxidative stress, and genetic factors. All these factors are intertwined with the dysregulation of myriad miRNAs. These microRNAs, as biomarkers, not only help in early diagnosis and disease monitoring, but may also become new therapeutic targets and provide new ideas for intervention strategies in Alzheimer’s disease. [miR microRNA, APP amyloid precursor protein, BACE1 beta-secretase 1, PS1/2 Presenilin1/2, TNF-α tumor necrosis factor α, IL interleukin, TGF-β transforming growth factor β, NF-κB nuclear factor Kappa B, SOCS suppressor of cytokine signaling, STAT signal transducer and activator of transcription, OH hydroxyl radical, O2 oxygen, NO nitric oxide, PHF paired helical filaments, NFT neurofibrillary tangle, SOD2 superoxide dismutase 2, GSK3β glycogen synthase kinase 3β, NCAM neural cell adhesion molecule, BCL-2 B-cell lymphoma-2, MFN2 mitochondrial fusion protein 2, MDH2 malate dehydrogenase, MCL1 myeloid cell leukemia 1, ERK1/2 extracellular regulated protein kinases1/2].
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