Company: APM
Filing Date: 2025-07-15
Form Type: DRS
Source: 0001213900-25-063899
Chunk: 267

Company: Aptorum Group Ltd
Filing Date: 2025-07-15
Form: DRS
Chunk 267
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 graph below captures the number of peer-reviewed papers listed on pubmed.ncbi.nih.gov on the role of miRNAs in AD by year,
increasing from 46 publications in 2012 to over 300 in 2022.

<div align='center'>https://pubmed.ncbi.nlm.nih.gov/?term=alzhemiers+microRNA</div>

Biology of miRNAs

miRNAs are a class of non-coding, approximately
22 nucleotide long, functional RNA molecules. They play important role in the regulation of gene expression by binding to complementary
regions of messenger RNA transcripts, the type that encode proteins, to regulate their translation to proteins or their degradation (Huang,
et al, J Physiol Biochem. 67, 129-39 (2011)). Frequently, one miRNA can target multiple messenger RNAs (mRNAs) and one mRNA can be regulated
by multiple miRNAs targeting different regions of the 3’ UTR (untranslated region). Once bound to an mRNA, miRNA can modulate protein
production by affecting mRNA translation and stability, and thus have a significant impact on cell biology and disease pathology. (Griffiths-Jones
et al., Nucleic Acids Res. 34, Database issue: D140–D144 (2006); Bartel, Cell 136, 215-233 (2009); Kim, Mol Cells 19, 1–15
(2005); Ha, et al., Nat Rev Mol Cell Biol. 15, 509–524 (2014); Roberts, Mol Ther Nucleic Acids 3:e188 (2014); Vishnoi, et al., Methods
Mol Biol. 2595, 1-12 (2023)).

<div align='center'>138</div>

Many miRNAs are specific to, or are over-expressed,
in certain organs and tissues, including different brain regions (such as hippocampus, midbrain, frontal cortex, pituitary gland), and
different cell types, such as neurons and glial cells (Landgraf, et al., Cell 129, 1401-1414 (2007); Liang, et al., BMC Genomics 8, 166
(2007); Lee, et al., RNA 14, 35-42 (2008); Sempere, et al., Genome Biol. 5, R13 (2004); Deo, et al