Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Oct 13:15:1043947.
doi: 10.3389/fnmol.2022.1043947. eCollection 2022.

Combinational treatments of RNA interference and extracellular vesicles in the spinocerebellar ataxia

Yingying Ding  1   2 , Yong Zhang  1 , Xuehong Liu  1
Affiliations
Review

Combinational treatments of RNA interference and extracellular vesicles in the spinocerebellar ataxia

Yingying Ding et al. Front Mol Neurosci. .

Abstract

Spinocerebellar ataxia (SCA) is an autosomal dominant neurodegenerative disease (ND) with a high mortality rate. Symptomatic treatment is the only clinically adopted treatment. However, it has poor effect and serious complications. Traditional diagnostic methods [such as magnetic resonance imaging (MRI)] have drawbacks. Presently, the superiority of RNA interference (RNAi) and extracellular vesicles (EVs) in improving SCA has attracted extensive attention. Both can serve as the potential biomarkers for the diagnosing and monitoring disease progression. Herein, we analyzed the basis and prospect of therapies for SCA. Meanwhile, we elaborated the development and application of miRNAs, siRNAs, shRNAs, and EVs in the diagnosis and treatment of SCA. We propose the combination of RNAi and EVs to avoid the adverse factors of their respective treatment and maximize the benefits of treatment through the technology of EVs loaded with RNA. Obviously, the combinational therapy of RNAi and EVs may more accurately diagnose and cure SCA.

Keywords: RNA interference; combinational treatment; extracellular vesicle; miRNA; neurodegenerative disease; shRNA; siRNA; spinocerebellar ataxia.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Transmission mechanism of polyQ protein. a. Error folding and aggregation of polyQ encoded protein. A. Extracellular vesicle pathway. B. Nano tunnel tube approach: the polyQ protein is exchanged by a tunnel-like membrane-derived structure that connects two cells. C. Soluble oligomer: due to its high solubility and small size, PolyQ protein may be able to escape from cells and diffuse to other cells. D. Synaptic connection: the polyQ protein is transmitted between neurons with high transmission efficiency.
FIGURE 2
FIGURE 2
Mechanism of the binding of EVs and miRNA in the treatment of SCA3. (A) Appropriately stimulate the specific metrocyte (such as hypoxia treatment) to maximize the therapeutic value of EVs derived from it. (B) Load the desired miRNA into the isolated and purified EVs through electroporation, incubation or ultrasound, etc. (C) EVs with specific miRNA acts on corresponding miRNA sites (there are 1,137 known sites presently) in the 3’UTR of mutant ATXN3 mRNA. (D) The mutated ATXN3 mRNA that binds to the miRNA in the 3’UTR region is degraded or its translation is inhibited. (E) Misfolding and aggregation of the mutated ATXN3 protein occur. Transcription factors are adsorbed by protein aggregates, interfering with the expression and biogenesis of normal miRNA. Eventually the neurons degenerate.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Agliardi C., Meloni M., Guerini F. R., Zanzottera M., Bolognesi E., Baglio F., et al. (2021). Oligomeric α-Syn and SNARE complex proteins in peripheral extracellular vesicles of neural origin are biomarkers for Parkinson’s disease. Neurobiol. Dis. 148:105185. 10.1016/j.nbd.2020.105185 - DOI - PubMed
    1. Aigner A. (2019). Perspectives, issues and solutions in RNAi therapy: The expected and the less expected. Nanomedicine (Lond) 14 2777–2782. 10.2217/nnm-2019-0321 - DOI - PubMed
    1. Akhilesh, Uniyal A., Gadepalli A., Tiwari V., Allani M., Chouhan D., et al. (2022). Unlocking the potential of TRPV1 based siRNA therapeutics for the treatment of chemotherapy-induced neuropathic pain. Life Sci. 288:120187. 10.1016/j.lfs.2021.120187 - DOI - PubMed
    1. Arioz B. I., Tufekci K. U., Olcum M., Durur D. Y., Akarlar B. A., Ozlu N., et al. (2021). Proteome profiling of neuron-derived exosomes in Alzheimer’s disease reveals hemoglobin as a potential biomarker. Neurosci. Lett. 755:135914. 10.1016/j.neulet.2021.135914 - DOI - PubMed
    1. Athauda D., Gulyani S., Karnati H. K., Li Y., Tweedie D., Mustapic M., et al. (2019). Utility of neuronal-derived exosomes to examine molecular mechanisms that affect motor function in patients with Parkinson disease: A secondary analysis of the Exenatide-PD trial. JAMA Neurol. 76 420–429. 10.1001/jamaneurol.2018.4304 - DOI - PMC - PubMed

LinkOut - more resources