Soares Ericks S, de Souza Ana C Guerra, Zanella Camila A, Carmichael Ruth E, Henley Jeremy M, Wilkinson Kevin A, Cimarosti Helena I
Postgraduate Program in Pharmacology, Federal University of Santa Catarina, Brazil.
School of Biochemistry, University of Bristol, UK.
IBRO Neurosci Rep. 2022 Jan 22;12:142-148. doi: 10.1016/j.ibneur.2022.01.003. eCollection 2022 Jun.
Defining the molecular changes that underlie Alzheimer's disease (AD) is an important question in neuroscience. Here, we examined changes in protein SUMOylation, and proteins involved in mitochondrial dynamics, in an in vitro model of AD induced by application of amyloid-β 1-42 (Aβ) to cultured neurons. We observed Aβ-induced decreases in global SUMOylation and in levels of the SUMO pathway enzymes SENP3, PIAS1/2, and SAE2. Aβ exposure also decreased levels of the mitochondrial fission proteins Drp1 and Mff and increased activation of caspase-3. To examine whether loss of SENP3 is cytoprotective we knocked down SENP3, which partially prevented the Aβ-induced increase in caspase-3 activation. Together, these data support the hypothesis that altered SUMOylation may play a role in the mechanisms underlying AD.
确定阿尔茨海默病（AD）潜在的分子变化是神经科学中的一个重要问题。在此，我们在将淀粉样β蛋白1-42（Aβ）应用于培养神经元所诱导的AD体外模型中，研究了蛋白质SUMO化以及参与线粒体动力学的蛋白质的变化。我们观察到Aβ诱导全局SUMO化以及SUMO途径酶SENP3、PIAS1/2和SAE2水平降低。Aβ暴露还降低了线粒体分裂蛋白Drp1和Mff的水平，并增加了caspase-3的激活。为了研究SENP3的缺失是否具有细胞保护作用，我们敲低了SENP3，这部分阻止了Aβ诱导的caspase-3激活增加。总之，这些数据支持了SUMO化改变可能在AD潜在机制中起作用这一假说。
