Das Pritam, Golde Todd
Department of Neuroscience, College of Medicine, Mayo Clinic, Jacksonville, Florida 32224, USA.
J Clin Invest. 2006 Nov;116(11):2855-7. doi: 10.1172/JCI30284.
Accumulation of beta-amyloid peptide (Abeta) in the brain is believed to trigger a complex and poorly understood pathologic reaction that results in the development of Alzheimer's disease (AD). Despite intensive study, there is no consensus as to how Abeta accumulation causes neurodegeneration in AD. In this issue of the JCI, Tesseur et al. report that the expression of TGF-beta type II receptor (TbetaRII) by neurons is reduced very early in the course of AD and that reduced TGF-beta signaling increased Abeta deposition and neurodegeneration in a mouse model of AD (see the related article beginning on page 3060). Intriguingly, reduced TGF-beta signaling in neuroblastoma cells resulted in neuritic dystrophy and increased levels of secreted Abeta. Collectively, these data suggest that dysfunction of the TGF-beta/TbetaRII signaling axis in the AD brain may accelerate Abeta deposition and neurodegeneration.
大脑中β-淀粉样肽（Aβ）的积累被认为会引发一种复杂且尚未完全理解的病理反应，进而导致阿尔茨海默病（AD）的发展。尽管进行了深入研究，但对于Aβ积累如何导致AD中的神经退行性变尚无共识。在本期《临床研究杂志》中，泰瑟尔等人报告称，在AD病程的早期，神经元中转化生长因子βII型受体（TβRII）的表达就会显著降低，并且在AD小鼠模型中，转化生长因子β信号的减少会增加Aβ沉积和神经退行性变（见第3060页开始的相关文章）。有趣的是，神经母细胞瘤细胞中转化生长因子β信号的减少会导致神经突营养不良，并增加分泌型Aβ的水平。总体而言，这些数据表明AD大脑中转化生长因子β/TβRII信号轴的功能障碍可能会加速Aβ沉积和神经退行性变。
