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Beta2-adrenoreceptor agonist clenbuterol produces transient decreases in alpha-synuclein mRNA but no long-term reduction in protein
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Beta2-adrenoreceptor agonist clenbuterol produces transient decreases in alpha-synuclein mRNA but no long-term reduction in protein
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Journal Article
Beta2-adrenoreceptor agonist clenbuterol produces transient decreases in alpha-synuclein mRNA but no long-term reduction in protein
2022
Overview
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
