Objective: Modulation of the β2-adrenoreceptor (also called the β2-adrenergic receptor or β2-adrenoceptor) has been reported to regulate SNCA expression. We sought to determine the expression of the β2-adrenoreceptor gene ADRB2 and the effects of β2-adrenoreceptor modulation on SNCA expression in cells closely resembling human dopaminergic neurons to evaluate the significance of this previously reported association.
Background: α-synuclein protein aggregation is central to the pathogenesis of Parkinson’s disease. Medications altering α-synuclein expression may thus have potential as neuroprotective treatments. β2-adrenoreceptor agonists have been reported to decrease α-synuclein mRNA and protein levels in human cell cultures and rodent neurons, and long-term use has been associated with reduced risk of developing Parkinson’s disease.
Method: We studied β2-adrenoreceptor RNA and protein levels in human dopaminergic neurons using gene expression assays and immunohistochemistry. α-synuclein expression levels were measured in dopaminergic LUHMES cells and SK-N-MC neuroblastoma cells treated with β2-adrenoreceptor agonists or antagonists.
Results: β2-adrenoreceptor RNA was expressed at very low levels in dopaminergic LUHMES cells and SK-N-MC neuroblastoma cells, and the protein was not present in dopaminergic neurons in human substantia nigra pars compacta. Treatment of dopaminergic LUHMES cells with β2-adrenoreceptor agonists (clenbuterol and salbutamol) and antagonist (propranolol) had no effect on α-synuclein expression. Similarly, SK-N-MC cells treated with clenbuterol and salbutamol showed no change in SNCA expression levels, whereas cell viability was severely affected by propranolol treatment.
Conclusion: β2-adrenoreceptor agonists or antagonists have no major effect on α-synuclein expression in human dopaminergic cells as they appear to lack β2-adrenoreceptors.
To cite this abstract in AMA style:
M. Langmyhr, IH. Flønes, CC. Cappelletti, C. Tzoulis, M. Toft. α-synuclein expression is not mediated by β2-adrenoreceptor modulation in human dopaminergic cells [abstract]. Mov Disord. 2021; 36 (suppl 1). https://www.mdsabstracts.org/abstract/%ce%b1-synuclein-expression-is-not-mediated-by-%ce%b22-adrenoreceptor-modulation-in-human-dopaminergic-cells/. Accessed June 16, 2025.« Back to MDS Virtual Congress 2021
MDS Abstracts - https://www.mdsabstracts.org/abstract/%ce%b1-synuclein-expression-is-not-mediated-by-%ce%b22-adrenoreceptor-modulation-in-human-dopaminergic-cells/