疫苗在预防即将到来的阿尔茨海默病流行中的重要性。

IF 1.4 Q4 PHARMACOLOGY & PHARMACY
Siddhant Tripathi, Yashika Sharma, Dileep Kumar
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引用次数: 0

摘要

使用抗体来中和细胞毒性可溶性淀粉样蛋白-β聚集体,而不是去除斑块,这给人们带来了谨慎的希望,因为单克隆抗体BAN2401似乎可以阻止前体阿尔茨海默病(AD)的病程。通过固定细胞毒性淀粉样蛋白-β,而不是致病因子,斑块可以帮助预防阿尔茨海默病。针对细胞毒性淀粉样蛋白-β的天然抗体显示出对阿尔茨海默病的预防性免疫。疫苗应包括促进抗炎Th2免疫的佐剂和预防不同细胞毒性淀粉样蛋白-β构象的免疫原,以预防或延缓阿尔茨海默病的发作。由于淀粉样蛋白-β多形性,单克隆抗体(如aducanumab)缺乏长期保护作用。在这种情况下,新的细胞毒性构象可能会逃避先前成功的单克隆抗体的中和。疫苗能否引发Th2极化免疫,取决于启动和同时向树突状细胞递送免疫原。除了中和针对神经毒性淀粉样蛋白-β寡聚物的抗体外,免疫反应还可能释放抗炎细胞因子,这有助于预防加剧阿尔茨海默病的炎症。由于与年龄相关的免疫功能下降,疫苗在预防阿尔茨海默病方面比治疗阿尔茨海默病要成功得多。由于淀粉样蛋白-β和tau蛋白都导致病理性过磷酸化,并协同作用导致阿尔茨海默病,因此应考虑对两者进行预防性接种。鉴于疫苗的可负担性和简单性,疫苗可能是阻止许多国家迫在眉睫的阿尔茨海默病大流行的唯一途径。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The Importance of Vaccines in Preventing Impending Alzheimer's Epidemic.

The use of antibodies to neutralize cytotoxic soluble amyloid-β aggregates rather than remove plaque has raised cautious hope since the monoclonal antibody BAN2401 seems to halt the course of prodromal Alzheimer's Disease (AD). By immobilizing cytotoxic amyloid-β, rather than the causative factor, plaques can help prevent Alzheimer's disease. A preventive immunity against Alzheimer's disease is shown by natural antibodies against cytotoxic amyloid-β. Vaccines should include adjuvants that promote anti-inflammatory Th2 immunity and immunogens that guard against different cytotoxic amyloid-β conformers to prevent or delay the onsetof Alzheimer's disease. The lack of long-term protection with monoclonal antibodies that neutralize single conformers, such as aducanumab, may be due to amyloid-β pleomorphism. In this scenario, novel cytotoxic conformers might evade neutralization by monoclonal antibodies that were previously successful. A vaccine's ability to elicit a polarized Th2 immunity would depend on both priming and the simultaneous delivery of immunogen to dendritic cells. In addition to neutralizing antibodies against neurotoxic amyloid-β oligomers, an immune response may also release anti-inflammatory cytokines, which can help prevent inflammation that exacerbates Alzheimer's disease. Vaccines would be significantly more successful in preventing Alzheimer's disease than treating it because of age-related immunological decrease. Since both amyloid-β and tau contribute to pathological hyperphosphorylation and work in tandem to cause Alzheimer's disease, preventive vaccinations against both should be taken into consideration. Given their affordability and simplicity, vaccines may be the only way to stop the looming Alzheimer's pandemic in many nations.

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来源期刊
Reviews on recent clinical trials
Reviews on recent clinical trials PHARMACOLOGY & PHARMACY-
CiteScore
3.10
自引率
5.30%
发文量
44
期刊介绍: Reviews on Recent Clinical Trials publishes frontier reviews on recent clinical trials of major importance. The journal"s aim is to publish the highest quality review articles in the field. Topics covered include: important Phase I – IV clinical trial studies, clinical investigations at all stages of development and therapeutics. The journal is essential reading for all researchers and clinicians involved in drug therapy and clinical trials.
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