Jarero-Basulto José J, Gasca-Martínez Yadira, Rivera-Cervantes Martha C, Gasca-Martínez Deisy, Carrillo-González Nidia Jannette, Beas-Zárate Carlos, Gudiño-Cabrera Graciela
Cellular Neurobiology Laboratory, Cell and Molecular Biology Department, University Center of Biological and Agricultural Sciences (CUCBA), University of Guadalajara, Zapopan 45220, Mexico;
Development and Neural Regeneration Laboratory, Cell and Molecular Biology Department, University Center of Biological and Agricultural Sciences (CUCBA), University of Guadalajara, Zapopan 45220, Mexico;
NeuroSci. 2024 May 7;5(2):141-157. doi: 10.3390/neurosci5020010. eCollection 2024 Jun.
Amyloid-β oligomers are a cytotoxic structure that is key for the establishment of the beginning stages of Alzheimer's disease (AD). These structures promote subcellular alterations that cause synaptic dysfunction, loss of cell communication, and even cell death, generating cognitive deficits. The aim of this study was to investigate the cytotoxic effects of amyloid-β1-42 oligomers (AβOs) on the membranous organelles involved in protein processing: the endoplasmic reticulum (ER) and Golgi apparatus (GA). The results obtained with 10 μM AβOs in SH-SY5Y neuroblastoma cells showed that oligomeric structures are more toxic than monomers because they cause cell viability to decrease as exposure time increases. Survivor cells were analyzed to further understand the toxic effects of AβOs on intracellular organelles. Survivor cells showed morphological alterations associated with abnormal cytoskeleton modification 72-96 h after exposure to AβOs. Moreover, the ER and GA presented rearrangement throughout the cytoplasmic space, which could be attributed to a lack of constitutive protein processing or to previous abnormal cytoskeleton modification. Interestingly, the disorganization of both ER and GA organelles exposed to AβOs is likely an early pathological alteration that could be related to aberrant protein processing and accumulation in AD.
淀粉样β寡聚体是一种细胞毒性结构，是阿尔茨海默病（AD）早期阶段形成的关键因素。这些结构会促进亚细胞改变，导致突触功能障碍、细胞间通讯丧失，甚至细胞死亡，进而产生认知缺陷。本研究的目的是调查淀粉样β1-42寡聚体（AβOs）对参与蛋白质加工的膜性细胞器——内质网（ER）和高尔基体（GA）的细胞毒性作用。在SH-SY5Y神经母细胞瘤细胞中用10μM AβOs获得的结果表明，寡聚体结构比单体毒性更大，因为随着暴露时间的增加，它们会导致细胞活力下降。对存活细胞进行分析，以进一步了解AβOs对细胞内细胞器的毒性作用。暴露于AβOs 72-96小时后，存活细胞表现出与异常细胞骨架修饰相关的形态改变。此外，内质网和高尔基体在整个细胞质空间呈现重排，这可能归因于组成型蛋白质加工的缺乏或先前异常的细胞骨架修饰。有趣的是，暴露于AβOs的内质网和高尔基体细胞器的紊乱可能是一种早期病理改变，可能与AD中异常的蛋白质加工和积累有关。
