Cuello A Claudio, Canneva Fabio
Department of Pharmacology and Therapeutics, McGill University, Montreal, Que., Canada.
Neurodegener Dis. 2008;5(3-4):146-8. doi: 10.1159/000113686. Epub 2008 Mar 6.
The present commentary based on cell and animal models of intracellular beta-amyloid (iAbeta) expression indicates that low levels of microscopically undetectable iAbeta could have a physiological role in the modulation of the cyclic AMP response element (CRE)-dependent gene expression and, as a consequence, a positive influence on synaptic plasticity (the 'good' Abeta?). On the other hand, high levels of iAbeta resembling the pathological and microscopically visible accumulation of this amyloid peptide, akin to that observed in Down syndrome and Alzheimer's disease, disrupt CRE-regulated gene expression, therefore compromising the protein synthesis-dependent component of long-term potentiation (the 'bad' Abeta?). Moreover, intracellular pathology would be independent and additive to the toxic effects of the extracellular Abeta burden.
基于细胞和细胞内β-淀粉样蛋白（iAbeta）表达的动物模型的本评论表明，低水平的显微镜下不可检测的iAbeta可能在调节环磷酸腺苷反应元件（CRE）依赖性基因表达中具有生理作用，因此，对突触可塑性有积极影响（“好的”Abeta？）。另一方面，高水平的iAbeta类似于这种淀粉样肽的病理和显微镜下可见的积累，类似于在唐氏综合征和阿尔茨海默病中观察到的情况，会破坏CRE调节的基因表达，从而损害长期增强的蛋白质合成依赖性成分（“坏的”Abeta？）。此外，细胞内病理将独立于细胞外Abeta负荷的毒性作用并与之相加。
