Instituto Teófilo Hernando, Universidad Autónoma de Madrid, Madrid, Spain.
Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain.
Pflugers Arch. 2018 Jan;470(1):187-198. doi: 10.1007/s00424-017-2044-5. Epub 2017 Aug 19.
In this review, we show how chromaffin cells have contributed to evaluate neuroprotective compounds with diverse mechanisms of action. Chromaffin cells are considered paraneurons, as they share many common features with neurons: (i) they synthesize, store, and release neurotransmitters upon stimulation and (ii) they express voltage-dependent calcium, sodium, and potassium channels, in addition to a wide variety of receptors. All these characteristics, together with the fact that primary cultures from bovine adrenal glands or chromaffin cells from the tumor pheochromocytoma cell line PC12 are easy to culture, make them an ideal model to study neurotoxic mechanisms and neuroprotective drugs. In the first part of this review, we will analyze the different cytotoxicity models related to calcium dyshomeostasis and neurodegenerative disorders like Alzheimer's or Parkinson's. Along the second part of the review, we describe how different classes of drugs have been evaluated in chromaffin cells to determine their neuroprotective profile in different neurodegenerative-related models.
在这篇综述中,我们展示了嗜铬细胞如何有助于评估具有不同作用机制的神经保护化合物。嗜铬细胞被认为是副神经节细胞,因为它们与神经元有许多共同特征:(i)它们在受到刺激时合成、储存和释放神经递质;(ii)它们表达电压依赖性钙、钠和钾通道,以及各种各样的受体。所有这些特征,加上牛肾上腺的原代培养物或肿瘤嗜铬细胞瘤细胞系 PC12 的嗜铬细胞很容易培养,使它们成为研究神经毒性机制和神经保护药物的理想模型。在本综述的第一部分,我们将分析与钙稳态失调和阿尔茨海默病或帕金森病等神经退行性疾病相关的不同细胞毒性模型。在综述的第二部分,我们描述了不同类别的药物在嗜铬细胞中的评估情况,以确定它们在不同与神经退行性相关的模型中的神经保护作用。