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MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After...
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Digestion begins with a cephalic phase that prepares the digestive system to receive food. When our brain processes visual or olfactory information about food, it triggers impulses in the cranial nerves innervating the salivary glands and stomach to prepare for food.
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MicroRNA-mRNA Regulatory Network Associated with Cognitive Impairment in Multiple Sclerosis.

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Cognitive impairment in multiple sclerosis (MS) is linked to specific microRNA (miRNA) changes. Identifying these miRNA signatures may aid in early detection and monitoring of MS-related cognitive dysfunction.

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Area of Science:

  • Neuroscience
  • Genetics
  • Biochemistry

Background:

  • Cognitive impairment (CI) is a significant disability in multiple sclerosis (MS).
  • The molecular mechanisms driving CI in MS are not fully understood.
  • MicroRNAs (miRNAs) are implicated in various neurological conditions.

Purpose of the Study:

  • To identify miRNA signatures and associated gene expression changes in MS patients with cognitive impairment.
  • To explore potential molecular pathways involved in MS-related CI.
  • To investigate the utility of miRNAs as biomarkers for cognitive dysfunction in MS.

Main Methods:

  • Collected peripheral blood mononuclear cells from 46 MS patients with varying cognitive function.
  • Performed miRNA profiling using PCR panels and validated with RT-qPCR.
  • Utilized bioinformatics tools (miRWalk, Cytoscape, STRING, DAVID) for target gene identification, network construction, and functional enrichment analysis.
  • Conducted gene expression analysis and correlation studies.

Main Results:

  • Three miRNAs (miR-146a-5p, miR-let-7a-5p, miR-21-5p) were significantly dysregulated in MS patients with CI.
  • Differential gene expression of IL-1B, IL-6, SLC16A10, and NEFL was observed, suggesting inflammatory and neurodegenerative pathways.
  • Specific miRNA-mRNA correlations were identified, linking molecular alterations to CI.

Conclusions:

  • Dysregulation of miR-146a-5p and miR-21-5p, along with their target genes, represents a molecular signature for CI in MS.
  • These findings highlight potential miRNA-based biomarkers for early diagnosis and monitoring of cognitive decline in MS.
  • Further research could leverage these molecular insights for therapeutic strategies.