Laboratory of Neurodegenerative Diseases, Facultad de Ciencias de La Salud, Instituto de Ciencias Biomédicas, Universidad Autónoma de Chile, Santiago, Chile.
Transl Neurodegener. 2022 Jul 4;11(1):36. doi: 10.1186/s40035-022-00308-y.
Neurological disorders (NDs) are characterized by progressive neuronal dysfunction leading to synaptic failure, cognitive impairment, and motor injury. Among these diseases, Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS) have raised a significant research interest. These disorders present common neuropathological signs, including neuronal dysfunction, protein accumulation, oxidative damage, and mitochondrial abnormalities. In this context, mitochondrial impairment is characterized by a deficiency in ATP production, excessive production of reactive oxygen species, calcium dysregulation, mitochondrial transport failure, and mitochondrial dynamics deficiencies. These defects in mitochondrial health could compromise the synaptic process, leading to early cognitive dysfunction observed in these NDs. Interestingly, skin fibroblasts from AD, PD, HD, and ALS patients have been suggested as a useful strategy to investigate and detect early mitochondrial abnormalities in these NDs. In this context, fibroblasts are considered a viable model for studying neurodegenerative changes due to their metabolic and biochemical relationships with neurons. Also, studies of our group and others have shown impairment of mitochondrial bioenergetics in fibroblasts from patients diagnosed with sporadic and genetic forms of AD, PD, HD, and ALS. Interestingly, these mitochondrial abnormalities have been observed in the brain tissues of patients suffering from the same pathologies. Therefore, fibroblasts represent a novel strategy to study the genesis and progression of mitochondrial dysfunction in AD, PD, HD, and ALS. This review discusses recent evidence that proposes fibroblasts as a potential target to study mitochondrial bioenergetics impairment in neurological disorders and consequently to search for new biomarkers of neurodegeneration.
神经紊乱（NDs）的特征是神经元功能逐渐失调，导致突触衰竭、认知障碍和运动损伤。在这些疾病中，阿尔茨海默病（AD）、帕金森病（PD）、亨廷顿病（HD）和肌萎缩侧索硬化症（ALS）引起了极大的研究兴趣。这些疾病具有共同的神经病理学特征，包括神经元功能障碍、蛋白质积累、氧化损伤和线粒体异常。在这种情况下，线粒体损伤的特征是 ATP 生成不足、活性氧过量产生、钙失调、线粒体运输失败和线粒体动力学缺陷。线粒体健康的这些缺陷可能会影响突触过程，导致这些 NDs 中早期认知功能障碍。有趣的是，AD、PD、HD 和 ALS 患者的皮肤成纤维细胞被认为是一种有用的策略，可以研究和检测这些 NDs 中的早期线粒体异常。在这种情况下，由于其与神经元的代谢和生化关系，成纤维细胞被认为是研究神经退行性变化的可行模型。此外，我们小组和其他小组的研究表明，患有散发性和遗传性 AD、PD、HD 和 ALS 的患者的成纤维细胞中线粒体生物能发生了损伤。有趣的是，这些线粒体异常在患有相同病理的患者的脑组织中也观察到。因此，成纤维细胞代表了一种研究 AD、PD、HD 和 ALS 中线粒体功能障碍发生和进展的新策略。这篇综述讨论了最近的证据，该证据提出成纤维细胞是研究神经紊乱中线粒体生物能障碍的潜在靶点，并寻找神经退行性变的新生物标志物。
