Rojas-Gutierrez Eduardo, Muñoz-Arenas Guadalupe, Treviño Samuel, Espinosa Blanca, Chavez Raúl, Rojas Karla, Flores Gonzalo, Díaz Alfonso, Guevara Jorge
Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de México, Mexico.
Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Puebla, Pue, Mexico.
Synapse. 2017 Oct;71(10):e21990. doi: 10.1002/syn.21990. Epub 2017 Aug 2.
Alzheimer's disease (AD) is the most common cause of dementia and one of the most important causes of morbidity and mortality among the aging population. AD diagnosis is made post-mortem, and the two pathologic hallmarks, particularly evident in the end stages of the illness, are amyloid plaques and neurofibrillary tangles. Currently, there is no curative treatment for AD. Additionally, there is a strong relation between oxidative stress, metabolic syndrome, and AD. The high levels of circulating lipids and glucose imbalances amplify lipid peroxidation that gradually diminishes the antioxidant systems, causing high levels of oxidative metabolism that affects cell structure, leading to neuronal damage. Accumulating evidence suggests that AD is closely related to a dysfunction of both insulin signaling and glucose metabolism in the brain, leading to an insulin-resistant brain state. Four drugs are currently used for this pathology: Three FDA-approved cholinesterase inhibitors and one NMDA receptor antagonist. However, wide varieties of antioxidants are promissory to delay or prevent the symptoms of AD and may help in treating the disease. Therefore, therapeutic efforts to achieve attenuation of oxidative stress could be beneficial in AD treatment, attenuating Aβ-induced neurotoxicity and improve neurological outcomes in AD. The term inflammaging characterizes a widely accepted paradigm that aging is accompanied by a low-grade chronic up-regulation of certain pro-inflammatory responses in the absence of overt infection, and is a highly significant risk factor for both morbidity and mortality in the elderly.
阿尔茨海默病（AD）是痴呆最常见的病因，也是老年人群发病和死亡的最重要原因之一。AD的诊断在尸检时做出，其两个病理特征在疾病末期尤为明显，即淀粉样斑块和神经原纤维缠结。目前，尚无针对AD的治愈性疗法。此外，氧化应激、代谢综合征与AD之间存在密切关联。循环脂质水平升高和葡萄糖失衡会加剧脂质过氧化，逐渐削弱抗氧化系统，导致高水平的氧化代谢，影响细胞结构，进而造成神经元损伤。越来越多的证据表明，AD与大脑中胰岛素信号传导和葡萄糖代谢功能障碍密切相关，导致大脑处于胰岛素抵抗状态。目前有四种药物用于治疗这种病症：三种获美国食品药品监督管理局（FDA）批准的胆碱酯酶抑制剂和一种N-甲基-D-天冬氨酸（NMDA）受体拮抗剂。然而，各种各样的抗氧化剂有望延缓或预防AD症状，可能有助于治疗该疾病。因此，减轻氧化应激的治疗措施可能对AD治疗有益，可减轻β-淀粉样蛋白（Aβ）诱导的神经毒性，并改善AD患者的神经学预后。“炎症衰老”一词描述了一种广泛接受的范式，即衰老伴随着在无明显感染情况下某些促炎反应的低度慢性上调，并且是老年人发病和死亡的高度显著风险因素。
