Maccioni Ricardo B, Navarrete Leonardo P, González Andrea, González-Canacer Alejandra, Guzmán-Martínez Leonardo, Cortés Nicole
Laboratory of Neuroscience and Functional Medicine, International Center for Biomedicine, Vitacura, Santiago, Chile, and Faculty of Sciences, University of Chile, Ñuñoa, Santiago, Chile.
J Alzheimers Dis. 2020;76(4):1199-1213. doi: 10.3233/JAD-191014.
Several hypotheses have been postulated to explain how Alzheimer's disease is triggered, but none of them provide a unified view of its pathogenesis. The dominant hypothesis based on build-ups of the amyloid-β peptide has been around for longer than three decades; however, up to today, numerous clinical trials based on the amyloid postulates have been attempted, but all of them have failed. Clearly, the revisited tau hypothesis provides a better explanation of the clinical observations of patients, but it needs to integrate the cumulative observations on the onset of this disease. In this context, the neuroimmuno modulation theory, based on the involvement of inflammatory events in the central nervous system, accounts for all these observations. In this review we intend to emphasize the idea that neuroinflammation is a main target for the search of new therapeutic strategies to control Alzheimer's disease. Beyond mono-targeting approaches using synthetic drugs that control only specific pathophysiological events, emerging therapeutics views based on multi targeting compounds appear to provide a new pathway for Alzheimer's disease treatment.
人们已经提出了几种假说来解释阿尔茨海默病是如何引发的，但没有一种能对其发病机制提供统一的观点。基于β淀粉样肽积累的主流假说已经存在了三十多年；然而，直到如今，许多基于淀粉样假说的临床试验都已尝试，但全部失败了。显然，重新审视的tau蛋白假说能更好地解释患者的临床观察结果，但它需要整合关于这种疾病发病的累积观察结果。在这种背景下，基于中枢神经系统炎症事件参与的神经免疫调节理论能解释所有这些观察结果。在这篇综述中，我们打算强调神经炎症是寻找控制阿尔茨海默病新治疗策略的主要靶点这一观点。除了使用仅控制特定病理生理事件的合成药物的单靶点方法外，基于多靶点化合物的新兴治疗观点似乎为阿尔茨海默病的治疗提供了一条新途径。
