摘要
全球受阿尔兹海默症(AD)影响大约的有4400万人,至今还没有治疗方案来阻止痴呆的发展。AD的神经病理学标志是在斑块、高度磷酸化的 tau蛋白形成缠结的内神经元积累和慢性炎症中组装的淀粉样蛋白β(Aβ)肽的细胞外沉积物。炎症中的关键分子是促炎细胞因子TNF-α。通过遗传和药理操纵的一些证据表明TNF-α信号在体内加剧Aβ和tau病理特征。有趣的是,抗炎策略的预防和干预在AD的啮齿类动物模型中显示脑病理特征的减少和认知功能的改善。I期和IIa期临床试验表明TNF-α抑制剂可能会减缓AD患者认知的降低和改善其日常活动。在本文,我们对通过抗TNF-α的作用来阻止或者减缓AD患者病情的恶化进行了综述,我们也陈述了在AD受试者中由于其局限性调节TNF-α信号所可能出现的物理的或者药理的干扰因素。
关键词: 阿尔兹海默症,BACE1,伊那西普,炎症,神经性炎症,沙利度胺,TNF-α
Current Alzheimer Research
Title:Targeting Tumor Necrosis Factor Alpha for Alzheimer’s Disease
Volume: 14 Issue: 4
关键词: 阿尔兹海默症,BACE1,伊那西普,炎症,神经性炎症,沙利度胺,TNF-α
摘要: 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 assembled in 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.
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Targeting Tumor Necrosis Factor Alpha for Alzheimer’s Disease, Current Alzheimer Research 2017; 14 (4) . https://dx.doi.org/10.2174/1567205013666160930110551
DOI https://dx.doi.org/10.2174/1567205013666160930110551 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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Alzheimer's disease (AD) poses a significant global health challenge, with an increasing number of individuals affected yearly. Deep learning, a subfield of artificial intelligence, has shown immense potential in various domains, including healthcare. This thematic issue of Current Alzheimer Research explores the application of deep learning techniques in advancing our ...read more
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