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Cited by 44Down syndrome and intellectual disability researchMicroRNA in disease regulationGenetics and Neurodevelopmental Disorders

Chromosome 21-Encoded microRNAs (mRNAs): Impact on Down’s Syndrome and Trisomy-21 Linked Disease

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Alexandrov, P. N., Percy, M. E., Lukiw, Walter J.·2018·Cellular and Molecular Neurobiology
DOI 10.1007/s10571-017-0514-0PMC PMC5756687
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Abstract

Down's syndrome (DS; also known as trisomy 21; T21) is caused by a triplication of all or part of human chromosome 21 (chr21). DS is the most common genetic cause of intellectual disability attributable to a naturally-occurring imbalance in gene dosage. DS incurs huge medical, healthcare, and socioeconomic costs, and there are as yet no effective treatments for this incapacitating human neurogenetic disorder. There is a remarkably wide variability in the 'phenotypic spectrum' associated with DS; the progression of symptoms and the age of DS onset fluctuate, and there is further variability in the biophysical nature of the chr21 duplication. Besides the cognitive disruptions and dementia in DS patients other serious health problems such as atherosclerosis, altered lipogenesis, Alzheimer's disease, amyotrophic lateral sclerosis (Lou Gehrig's disease), autoimmune disease, various cancers including lymphoma, leukemia, glioma and glioblastoma, status epilepticus, congenital heart disease, hypotonia, manic depression, prostate cancer, Usher syndrome, motor disorders, Hirschsprung disease, and various physical anomalies such as early aging occur at elevated frequencies, and all are part of the DS 'phenotypic spectrum.' This communication will review the genetic link between these fore-mentioned diseases and a small group of just five stress-associated microRNAs (miRNAs)-that include let-7c, miRNA-99a, miRNA-125b, miRNA-155, and miRNA-802-encoded and clustered on the long arm of human chr21 and spanning the chr21q21.1-chr21q21.3 region.

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  • As one of five miRNAs located on chromosome 21 flanking the APP gene, pathological implications of additional copies of miR-155 extend beyond inflammatory regulation and have gained interest in Trisomy-21 and AD pathogenesis.

    “As one of the five miRNAs located on chromosome 21 flanking the APP gene, the pathological implications of additional copies of miR-155 extend beyond inflammatory regulation and have gained interest and attention in Trisomy-21 and AD pathogenesis [49, 50].”

    From Microglia specific deletion of miR-155 in Alzheimer’s disease mouse models reduces amyloid-β pathology but causes hyperexcitability and seizures (2023) · cites this paper as [49]

    The Introduction identifies miR-155 as one of five chromosome 21 miRNAs clustered in the region that also contains APP, and links increased miR-155 dosage to pathogenic signaling in Down syndrome and Alzheimer’s disease. Its specific account of miR-155 concerns complement factor H and inflammatory neurodegeneration; it does not establish a role for miR-155 in those diseases beyond inflammatory regulation. (LLM, conf=0.82)

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Cited by

Sorted by citations

Authors
Alexandrov, P. N., Percy, M. E., & Lukiw, W. J.
Affiliations
  • University of Toronto (CA)
  • Louisiana State University (US)
Corresponding author
Lukiw, Walter J.
ORCID
Lukiw, Walter J.
Venue
Cellular and Molecular Neurobiology
Publisher
Springer Science and Business Media LLC
Published
2017-07-07
Volume
38
Issue
3
Pages
769-774
ISSN
  • 0272-4340 (ISSN-L)
  • 1573-6830
DOI
10.1007/s10571-017-0514-0
PMC
PMC5756687
OpenAlex
W2725737780
Cited by
44
References
0
Citations by year
2026: 1 · 2025: 3 · 2024: 12 · 2023: 4 · 2022: 5 · 2021: 8 · 2020: 2 · 2019: 6 · 2018: 1 · 2017: 2
FWCI
2.82
Type
journal article
Language
en
Open access
Licence
Locations
  • Cellular and Molecular Neurobiology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
Funders
  • National Institute on Aging (NIA AG038834, NIA AG18031)
  • National Eye Institute (NEI EY006311)
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Keywords
Down syndrome, chromosome 21, microRNA, let-7c, miR-99a, miR-125b, miR-155, miR-802, phenotypic variability, intellectual disability, Alzheimer's disease, amyotrophic lateral sclerosis, cancer susceptibility, autoimmune disease
MeSH terms
Alzheimer Disease, Chromosomes, Human, Pair 21, Down Syndrome, Humans, Memory, Trisomy, Gene Dosage, MicroRNAs

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