Beta2-adrenoreceptor agonist clenbuterol produces transient decreases in alpha-synuclein mRNA but no long-term reduction in protein.
Beta2-adrenoreceptor agonist clenbuterol produces transient decreases in alpha-synuclein mRNA but no long-term reduction in protein.
复制标题
β2-肾上腺素受体激动剂clenbuterol会在α-核蛋白mRNA中产生短暂的降低，但蛋白质的长期降低没有。
DOI：
10.1038/s41531-022-00322-x
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发表时间：
2022-05-24
影响因子：
8.7
通讯作者：
Sortwell, Caryl E.
中科院分区：
文献类型：
--
作者：
Patterson, Joseph R.;Hirst, Warren D.;Howe, Jacob W.;Russell, Christopher P.;Cole-Strauss, Allyson;Kemp, Christopher J.;Duffy, Megan F.;Lamp, Jared;Umstead, Andrew;Kubik, Michael;Stoll, Anna C.;Vega, Irving E.;Steece-Collier, Kathy;Chen, Yi;Campbell, Anne C.;Nezich, Catherine L.;Glajch, Kelly E.;Sortwell, Caryl E.
β2-肾上腺素受体（β2AR）激动剂与帕金森病（PD）发病风险降低相关，并被推测可降低α-突触核蛋白mRNA （Snca）和蛋白（α-syn）的表达。通过两个独立的实验室研究了β2AR激动剂盐酸克仑特罗对体内（大鼠和小鼠）和大鼠初级皮质神经元中Snca mRNA和α-syn蛋白水平的影响。大鼠在单次急性剂量盐酸克仑特罗后观察到黑质Snca mRNA的适度减少，然而，多次剂量后这种减少不能维持。相比之下，α-syn蛋白水平在单次和多次给药模式下都没有变化。此外，盐酸克仑特罗不降低培养大鼠皮层原代神经元中Snca含量，也不降低小鼠中Snca和α-syn含量。此外，与单次给药相比，重复给药可显著降低啮齿动物血浆和脑组织中的盐酸克仑特罗水平。根据我们在临床前研究中观察到的Snca的短暂下降和α-syn蛋白的无影响，这些数据支持克仑特罗不太可能是PD的可行疾病改善策略的结论。
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.
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影响因子：
82.9
作者：
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通讯作者：
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作者：
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