| Autor: |
Joseph R. Patterson, Warren D. Hirst, Jacob W. Howe, Christopher P. Russell, Allyson Cole-Strauss, Christopher J. Kemp, Megan F. Duffy, Jared Lamp, Andrew Umstead, Michael Kubik, Anna C. Stoll, Irving E. Vega, Kathy Steece-Collier, Yi Chen, Anne C. Campbell, Catherine L. Nezich, Kelly E. Glajch, Caryl E. Sortwell |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
npj Parkinson's Disease, Vol 8, Iss 1, Pp 1-14 (2022) |
| Druh dokumentu: |
article |
| ISSN: |
2373-8057 |
| DOI: |
10.1038/s41531-022-00322-x |
| Popis: |
Abstract β2-adrenoreceptor (β2AR) agonists have been associated with a decreased risk of developing Parkinson’s disease (PD) and are hypothesized to decrease expression of both alpha-synuclein mRNA (Snca) and protein (α-syn). Effects of β2AR agonist clenbuterol on the levels of Snca mRNA and α-syn protein were evaluated in vivo (rats and mice) and in rat primary cortical neurons by two independent laboratories. A modest decrease in Snca mRNA in the substantia nigra was observed after a single acute dose of clenbuterol in rats, however, this decrease was not maintained after multiple doses. In contrast, α-syn protein levels remained unchanged in both single and multiple dosing paradigms. Furthermore, clenbuterol did not decrease Snca in cultured rat primary cortical neurons, or decrease Snca or α-syn in mice. Additionally, compared to the single-dose paradigm, repeat dosing resulted in substantially lower levels of clenbuterol in plasma and brain tissue in rodents. Based on our observations of a transient decrease in Snca and no effect on α-syn protein in this preclinical study, these data support the conclusion that clenbuterol is not likely a viable disease-modifying strategy for PD. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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