Study on the Therapeutic Effect of shRNA Injected into Tail Vein on Parkinson’s Disease in Mice Based on SNCA Gene Mutation of α-Synuclein

Yutong Zhang; Xiuzhi Dai

doi:10.62051/9ce7yb40

Authors

Yutong Zhang
Xiuzhi Dai

DOI:

https://doi.org/10.62051/9ce7yb40

Keywords:

shRNA; α-Synuclein; Parkinson’s Disease; SNCA Gene.

Abstract

Aim: This research aims to investigate the therapeutic effect of shRNA injected into the tail vein on Parkinson’s disease in mice based on SNCA gene mutation of α-synuclein and explore the migration mechanism of α-synuclein. Methods: SCNA +/+ mice are used to induce α-synuclein by tuberculin pff and then establish the model of Parkinson’s disease in mice. Besides, AAV-shRNA is used to set the control group and the experimental group at different times. Open-field test, tail suspension test, and immunofluorescence are adopted to explore the therapeutic effect of shRNA and the migration mechanism of α-synuclein. Results: shRNA inhibits P-α-syn in the brain of mice afflicted with Parkinson’s disease, which has obvious behavioral therapy. The whole brain invasion of α-synuclein in OB of the olfactory bulb occurs, while the invasion of α-synuclein in CPu of the dorsal striatum only exists in the downstream brain region. Conclusion: Intravenous injection of shRNA into the tail vein can effectively inhibit α-synuclein with symptomatic therapeutic effect on mice with Parkinson’s disease, and the earlier injection enables better therapeutic effect.

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References

Ascherio, A. & Schwarzschild, M. A. (2016). The epidemiology of Parkinson’s case: Risk factors and prevention. Lancet Neurol, 15(12): 1257-1272. doi: 10.1016/S1474-4422 (16) 30230-7. Epub 2016 Oct 11. PMID: 27751556.

Cacabelos, R. (2017). Parkinson’s disease: From pathogenesis to pharmacogenomics. Int J Mol Sci, 18(3): 551. doi: 10.3390/ijms18030551. PMID: 28273839; PMCID: PMC5372567.

de Lau, L. M. & Breteler, M. M. (2006). Epidemiology of Parkinson’s disease. Lancet Neurol, 5(6): 525-35. doi: 10.1016/S1474-4422 (06) 70471-9. PMID: 16713924.

Dickson, D. W., Braak, H., Duda, J. E., Duyckaerts, C., Gasser, T., Halliday, G. M., Hardy, J., Leverenz, J. B., Del Tredici, K., Wszolek, Z. K. & Litvan, I. (2010). Neuropathological assessment of Parkinson’s disease: Refining the diagnostic criteria. Lancet Neurol, 8(12): 1150-7. doi: 10.1016/S1474-4422 (09) 70238-8. Erratum in: Lancet Neurol. 2010 Feb, 9(2): 140. Erratum in: Lancet Neurol, 2010 Jan, 9(1): 29. PMID: 19909913.

Dorsey, E. R., Constantinescu, R., Thompson, J. P., Biglan, K. M., Holloway, R. G., Kieburtz, K., Marshall, F. J., Ravina, B. M., Schifitto, G., Siderowf, A. & Tanner, C. M. (2007). Project number of people with Parkinson’s disease in the most popular nations, 2005 through 2030. Neurology, 68(5): 384-6. doi: 10.1212/01.wnl.00024774 0. 47667. 03. Epub 2006 Nov 2. PMID: 17082464.

Guiney, S. J., Adlard, P. A., Lei, P., Mawal, C. H., Bush, A. I., Finkelstein, D. I. & Ayton, S. (2020). Fibrillar α-synuclein tool dependencies on functional lysosomes. J Biol Chem, 295(51): 17497-17513. doi: 10.1074/jbc.RA120.013428. PMID: 3345399 4; PMCID: PMC7762966.

Luk, K. C., Kehm, V. M., Zhang, B., O’Brien, P., Trojanowski, J. Q. & Lee, V. M. (2012). Intracerebral inoculation of pathological α-synuclein initiates a rapidly progressive neurodevelopmental α-synucleinopathy in mice. J Exp Med, 209(5): 975-86. doi: 10.1084/jem.20112457. Epub 2012 Apr 16. PMID: 22508839; PMCID: PMC 3348112.

Spillantini, M. G., Schmidt, M. L., Lee, V. M., Trojanowski, J. Q., Jakes, R. & Goedert, M. (1997). Alpha-synuclein in Lewy bodies. Nature, 388 (6645): 839-40. doi: 10.1038/42166. PMID: 9278044.