澱粉樣β蛋白和tau蛋白在阿爾茨海默氏病中的協同作用
作者:
小柯機器人發布時間:2020/8/13 17:14:04
近日,英國倫敦大學學院Marc Aurel Busche等研究人員總結了澱粉樣β蛋白和tau蛋白在阿爾茨海默氏病中的協同作用。2020年8月10日,國際知名學術期刊《自然—神經科學》在線發表了這一論文。
研究人員表示,阿爾茨海默氏病(AD)患者在大腦中同時存在細胞外澱粉樣β(Aβ)斑塊和含有胞內tau的神經原纖維纏結。多年來,AD發病機理的主要觀點是,Aβ的變化會加速疾病進程並引發涉及tau病理和神經變性的有害級聯反應。除了此「觸發」功能外,通常還認為Aβ和tau在沒有特定相互作用的情況下獨立發揮作用。
但是,現在越來越多的證據表明存在其他問題,並認為這兩種病理都有協同作用。這不僅有助於解釋抗Aβ臨床試驗的負面結果,而且還暗示可能需要重新考慮僅針對tau的試驗。
從廣泛的人類和疾病模型數據中,研究人員重點總結了與複雜的Aβ-tau相互作用有關的最新證據,並強調了其在闡明疾病發病機理和設計下一代AD治療試驗中的重要意義。
附:英文原文
Title: Synergy between amyloid-β and tau in Alzheimer’s disease
Author: Marc Aurel Busche, Bradley T. Hyman
Issue&Volume: 2020-08-10
Abstract: Patients with Alzheimer’s disease (AD) present with both extracellular amyloid-β (Aβ) plaques and intracellular tau-containing neurofibrillary tangles in the brain. For many years, the prevailing view of AD pathogenesis has been that changes in Aβ precipitate the disease process and initiate a deleterious cascade involving tau pathology and neurodegeneration. Beyond this 『triggering』 function, it has been typically presumed that Aβ and tau act independently and in the absence of specific interaction. However, accumulating evidence now suggests otherwise and contends that both pathologies have synergistic effects. This could not only help explain negative results from anti-Aβ clinical trials but also suggest that trials directed solely at tau may need to be reconsidered. Here, drawing from extensive human and disease model data, we highlight the latest evidence base pertaining to the complex Aβ–tau interaction and underscore its crucial importance to elucidating disease pathogenesis and the design of next-generation AD therapeutic trials.
DOI: 10.1038/s41593-020-0687-6
Source: https://www.nature.com/articles/s41593-020-0687-6