Regulation of alpha-synuclein expression through beta-2-adrenoreceptor agonists: a novel approach towards treating Parkinson's disease

• Main Author: Long, Elizabeth Keating
• Language: en_US
• Published: 2016
• Subjects: Neurosciences; Parkinson's disease; Alpha-synuclein
• Online Access: https://hdl.handle.net/2144/16203

The population of patients with Parkinson's disease, already the second most common neurodegenerative disorder, is continuing to grow. Despite years of research, no cure or clear pathogenic pathway has been discovered. However, the SNCA gene and its protein product, α-synuclein, have emerged as an important focus in both inherited and sporadic Parkinson's disease. Dosage effects created by duplication and triplication of the SNCA locus can cause the death of dopaminergic neurons in the brain. Naturally occurring overexpression of α-synuclein has been found to have the same devastating consequences. Most current drug development has focused on alleviating the overproduction of α-synuclein, instead of stopping it. We have hypothesized that by repressing endogenous SNCA gene expression at the transcription level we can prevent overexpression of α-synuclein and its associated toxicity. The discovery that β2-agonists, specifically clenbuterol hydrochloride, can reduce SNCA mRNA abundance and protein expression has implicated the β2-adrenergic receptor pathway as a potential regulatory target. We have further found that clenbuterol causes hypoaceytlation of histone H3 that may downregulate SNCA expression. Although, the precise mechanism by which β2-agonists are regulating SNCA expression needs to be further explained, our findings present exciting data that could potentially lead to a novel treatment for not just Parkinson's disease, but other synucleinopathies as well. === 2023-04-30