Borghi Roberta, Patriarca Stefania, Traverso Nicola, Piccini Alessandra, Storace Daniela, Garuti Anna
Department of Neuroscience, Ophthalmology and Genetics, University of Genova, Via De Toni 5, 16132 Genova, Italy.
Neurobiol Aging. 2007 Jul;28(7):1009-14. doi: 10.1016/j.neurobiolaging.2006.05.004.
We evaluated expression, protein levels and activity of the Beta-site cleaving enzyme (BACE1) as well as the amount of products of lipid peroxidation in frontal cortex of three groups of cases: sporadic Alzheimer's disease (AD); control subjects (CTR); cognitively normal subjects with abundant amyloid plaques (NA). We found a significant increase of BACE1 activity and products of lipid peroxidation in brain tissue of AD cases, with normal gene expression, and non-significant elevation of protein levels. CTR and NA samples showed similar levels of BACE1 activity and oxidative products. BACE1 activity and the amount of oxidative products were significantly correlated in all cases.Moreover, both BACE1 activity and the level of 4-hydroxynonenal were correlated with the amount of Beta-amyloid pyroglutamated 3-42, the more toxic Beta-amyloid peptide that is characteristic of AD. These findings suggest that BACE1 activity reflects the type of ABeta species, rather than the Beta-amyloid plaques load. Hence, the increase of BACE1 activity occurring in sporadic AD is likely the effect, rather the cause, of ABeta accumulation and oxidative stress.
我们评估了三组病例额叶皮质中β-位点裂解酶（BACE1）的表达、蛋白水平和活性，以及脂质过氧化产物的量，这三组病例分别为：散发性阿尔茨海默病（AD）；对照受试者（CTR）；有大量淀粉样斑块的认知正常受试者（NA）。我们发现，AD病例脑组织中BACE1活性和脂质过氧化产物显著增加，基因表达正常，蛋白水平升高不显著。CTR和NA样本显示出相似水平的BACE1活性和氧化产物。在所有病例中，BACE1活性与氧化产物量显著相关。此外，BACE1活性和4-羟基壬烯醛水平均与焦谷氨酸化β-淀粉样蛋白3-42的量相关，焦谷氨酸化β-淀粉样蛋白3-42是AD特有的毒性更强的β-淀粉样肽。这些发现表明，BACE1活性反映的是Aβ种类的类型，而非β-淀粉样斑块负荷。因此，散发性AD中出现的BACE1活性增加可能是Aβ积累和氧化应激的结果，而非原因。
