Fanlo-Ucar Hugo, Picón-Pagès Pol, Herrera-Fernández Víctor, Ill-Raga Gerard, Muñoz Francisco J
Laboratory of Molecular Physiology, Department of Medicine and Life Sciences, Faculty of Medicine and Life Sciences, Universitat Pompeu Fabra, 08003 Barcelona, Spain.
Laboratory of Molecular and Cellular Neurobiotechnology, Institute of Bioengineering of Catalonia (IBEC), 08028 Barcelona, Spain.
Antioxidants (Basel). 2024 Oct 8;13(10):1208. doi: 10.3390/antiox13101208.
Alzheimer's disease (AD) is a progressive neurodegenerative disease, and it is currently the seventh leading cause of death worldwide. It is characterized by the extracellular aggregation of the amyloid β-peptide (Aβ) into oligomers and fibrils that cause synaptotoxicity and neuronal death. Aβ exhibits a dual role in promoting oxidative stress and inflammation. This review aims to unravel the intricate connection between these processes and their contribution to AD progression. The review delves into oxidative stress in AD, focusing on the involvement of metals, mitochondrial dysfunction, and biomolecule oxidation. The distinct yet overlapping concept of nitro-oxidative stress is also discussed, detailing the roles of nitric oxide, mitochondrial perturbations, and their cumulative impact on Aβ production and neurotoxicity. Inflammation is examined through astroglia and microglia function, elucidating their response to Aβ and their contribution to oxidative stress within the AD brain. The blood-brain barrier and oligodendrocytes are also considered in the context of AD pathophysiology. We also review current diagnostic methodologies and emerging therapeutic strategies aimed at mitigating oxidative stress and inflammation, thereby offering potential treatments for halting or slowing AD progression. This comprehensive synthesis underscores the pivotal role of Aβ in bridging oxidative stress and inflammation, advancing our understanding of AD and informing future research and treatment paradigms.
阿尔茨海默病（AD）是一种进行性神经退行性疾病，目前是全球第七大死因。其特征是淀粉样β肽（Aβ）在细胞外聚集成寡聚体和原纤维，导致突触毒性和神经元死亡。Aβ在促进氧化应激和炎症方面具有双重作用。本综述旨在揭示这些过程之间的复杂联系及其对AD进展的影响。该综述深入探讨了AD中的氧化应激，重点关注金属的参与、线粒体功能障碍和生物分子氧化。还讨论了硝基氧化应激这一独特但相互重叠的概念，详细阐述了一氧化氮的作用、线粒体扰动及其对Aβ产生和神经毒性的累积影响。通过星形胶质细胞和小胶质细胞功能研究炎症，阐明它们对Aβ的反应及其对AD脑内氧化应激的影响。在AD病理生理学背景下也考虑了血脑屏障和少突胶质细胞。我们还综述了当前旨在减轻氧化应激和炎症的诊断方法和新兴治疗策略，从而为阻止或减缓AD进展提供潜在治疗方法。这种全面的综合强调了Aβ在连接氧化应激和炎症方面的关键作用，增进了我们对AD的理解，并为未来的研究和治疗模式提供了信息。
