Cited by 225Cancer-related molecular mechanisms researchMicroRNA in disease regulationNeuroinflammation and Neurodegeneration Mechanisms

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Functional roles and networks of non-coding RNAs in the pathogenesis of neurodegenerative diseases

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Wu, Yi-Ying, Kuo, Hung-Chih·2020·Journal of Biomedical Science

DOI 10.1186/s12929-020-00636-zPMC PMC7140545

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Abstract

Recent transcriptome analyses have revealed that noncoding RNAs (ncRNAs) are broadly expressed in mammalian cells and abundant in the CNS, with tissue and cell type-specific expression patterns. Moreover, ncRNAs have been found to intricately and dynamically regulate various signaling pathways in neurodegeneration. As such, some antisense transcripts and microRNAs are known to directly affect neurodegeneration in disease contexts. The functions of ncRNAs in pathogenesis are unique for each disorder, as are the pertinent networks of ncRNA/miRNA/mRNA that mediate these functions. Thus, further understanding of ncRNA biogenesis and effects might aid the discovery of diagnostic biomarkers or development of effective therapeutics for neurodegenerative disorders. Here, we review the ncRNAs that have so far been identified in major neurodegenerative disease etiology and the mechanisms that link ncRNAs with disease-specific phenotypes, such as HTT aggregation in HD, α-synuclein in PD, and Aβ plaques and hyperphosphorylated Tau in AD. We also summarize the known lncRNA/miRNA/mRNA networks that participate in neurodegenerative diseases, and we discuss ncRNA-related treatments shown to delay disease onset and prolong lifespan in rodent models.

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Fig. 1 Cellular functions of ncRNAs involved in HD pathogenesis. (a) LncRNAs regulate mutant Htt induced neurotoxicity. (b) Networks of mutant Htt, microRNAs and mRNAs regulate neurotoxicity in HD. LncRNAs are shown in red, mRNA are shown in green and microRNAs are shown in blueCC BY · PubMed Central

Fig. 2 Cellular functions of ncRNAs involved in PD pathogenesis. (a) ncRNAs affect α-synuclein formation, which is linked to loss of dopaminergic (DA) neurons. (b) ncRNAs regulate apoptotic pathways leading to DA neuron degeneration. (c) ncRNAs regulate mitochondrial dysfunction. (d) ncRNAs regulates DA neuron viabilityCC BY · PubMed Central

Fig. 3 ncRNAs involved in APP expression and Aβ accumulation in AD. (a) ncRNAs promote APP expression (b) ncRNAs promote Aβ accumulation. (c) ncRNAs regulate BACE-1 function and Aβ secretionCC BY · PubMed Central

Fig. 4 Cellular functions of ncRNAs that regulate pTau and cell death in AD pathogenesis. (a) ncRNAs promote kinase activity and pTau accumulation. (b) ncRNAs promote cellular pathways leading to neurodegeneration in ADCC BY · PubMed Central

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Authors: Wu, Y.-Y., & Kuo, H.-C.
Affiliations: Institute of Cellular and Organismic Biology, Academia Sinica (TW)
National Taiwan University (TW)
Corresponding author: Kuo, Hung-Chih
ORCID: Wu, Yi-Ying
Venue: Journal of Biomedical Science
Publisher: Springer Science and Business Media LLC
Published: 2020-04-07
Volume: 27
Issue: 1
Pages: 49-49
ISSN: 1021-7770 (ISSN-L)
1423-0127
DOI: 10.1186/s12929-020-00636-z
PMC: PMC7140545
OpenAlex: W3015066166
Cited by: 213
References: 161
Citations by year: 2026: 8 · 2025: 22 · 2024: 39 · 2023: 54 · 2022: 35 · 2021: 43 · 2020: 11
FWCI: 3.95
Type: journal article
Language: en
Open access: diamond
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor)
Locations: Journal of Biomedical Science (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: Academia Sinica (AS-106-TP-B13, AS-SUMMIT-108)
Ministry of Science and Technology (MOST 106-0210-01-15-02, 108-3114-Y-001-002, MOST 107-0210-01-19-01)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords: non-coding RNA, neurodegenerative diseases, long non-coding RNA, microRNA, antisense transcripts, lncRNA-miRNA-mRNA network, Huntington's disease, alpha-synuclein, Parkinson's disease, Alzheimer's disease, amyloid plaques, tau hyperphosphorylation, disease biomarkers
MeSH terms: Animals, Humans, Biomarkers, Neurodegenerative Diseases, Gene Expression Profiling, RNA, Untranslated, Mice, Rats

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Functional roles and networks of non-coding RNAs in the pathogenesis of neurodegenerative diseases

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