Targeting Tumor Necrosis Factor Alpha for Alzheimer's Disease.
Targeting Tumor Necrosis Factor Alpha for Alzheimer's Disease.
复制标题
针对阿尔茨海默病的肿瘤坏死因子α。
DOI：
10.2174/1567205013666160930110551
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发表时间：
2017
影响因子：
2.1
通讯作者：
Sabbagh MN
中科院分区：
文献类型：
--
作者：
Decourt B;Lahiri DK;Sabbagh MN
阿尔茨海默氏病（AD）影响着全球约4400万人，但没有治疗干预可用于阻止痴呆症的进展。AD的神经病理学标志是淀粉样蛋白β（Aβ）肽在细胞外沉积到斑块中，过度磷酸化的tau蛋白在神经元内积聚形成缠结，以及慢性炎症。炎症中的关键分子是促炎细胞因子TNF-α。使用遗传学和药理学操作的几条证据表明，TNF-α信号转导在体内加重Aβ和tau病理。有趣的是，预防性和干预性抗炎策略在AD的啮齿动物模型中表现出脑病理学的减少和认知功能的改善。I期和IIa期临床试验表明，TNF-α抑制剂可能减缓AD患者的认知功能下降，改善日常活动。在本综述中，我们总结了抗TNF-α治疗对预防或减缓AD进展的有益作用的证据。我们还提出了可能的物理和药理学干预措施，以调节TNF-α信号在AD受试者沿着与他们的局限性。
Alzheimer’s disease (AD) affects an estimated 44 million individuals worldwide, yet no therapeutic intervention is available to stop the progression of the dementia. Neuropathological hallmarks of AD are extracellular deposits of amyloid beta (Aβ) peptides into plaques, intraneuronal accumulation of hyperphosphorylated tau protein forming tangles, and chronic inflammation. A pivotal molecule in inflammation is the pro-inflammatory cytokine TNF-α. Several lines of evidence using genetic and pharmacological manipulations indicate that TNF-α signaling exacerbates both Aβ and tau pathologies in vivo. Interestingly, preventive and intervention anti-inflammatory strategies demonstrated a reduction in brain pathology and an amelioration of cognitive function in rodent models of AD. Phase I and IIa clinical trials suggest that TNF-α inhibitors might slow down cognitive decline and improve daily activities in AD patients. In the present review, we summarize the evidence pointing towards a beneficial role of anti-TNF-α therapies to prevent or slow the progression of AD. We also present possible physical and pharmacological interventions to modulate TNF-α signaling in AD subjects along with their limitations.