Beta2-adrenoreceptor agonist clenbuterol produces transient decreases in alpha-synuclein mRNA but no long-term reduction in protein

Bibliographic Details
Title: Beta2-adrenoreceptor agonist clenbuterol produces transient decreases in alpha-synuclein mRNA but no long-term reduction in protein
Authors: 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
Source: npj Parkinson's Disease, Vol 8, Iss 1, Pp 1-14 (2022)
Publisher Information: Nature Portfolio, 2022.
Publication Year: 2022
Collection: LCC:Neurology. Diseases of the nervous system
Subject Terms: Neurology. Diseases of the nervous system, RC346-429
More Details: 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.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 2373-8057
Relation: https://doaj.org/toc/2373-8057
DOI: 10.1038/s41531-022-00322-x
Access URL: https://doaj.org/article/1490e19ae927454fbbfea97a835eff52
Accession Number: edsdoj.1490e19ae927454fbbfea97a835eff52
Database: Directory of Open Access Journals
More Details
ISSN:23738057
DOI:10.1038/s41531-022-00322-x
Published in:npj Parkinson's Disease
Language:English