Conformationally altered p53: a novel Alzheimer's disease marker?
Conformationally altered p53: a novel Alzheimer's disease marker?
复制标题
DOI：
10.1038/sj.mp.4002060
复制
发表时间：
2008-06-01
影响因子：
11
通讯作者：
Uberti, D.
中科院分区：
文献类型：
--
作者：
Lanni, C.;Racchi, M.;Uberti, D.
识别阿尔茨海默病(AD)的生物标志物对于提高诊断的准确性和/或监测推定治疗的有效性是非常有用的。在这方面，外周细胞可能非常重要，因为它们很容易接触到。根据诊断将受试者分组后，通过免疫沉淀法或细胞荧光法比较血细胞中构象突变p53的表达。总共分析了104名AD患者、92名年龄匹配的对照组、15名帕金森病患者和9名其他类型的痴呆症患者。建立了两种独立的方法来评估构象突变型P53的差异表达。通过免疫沉淀或流式细胞仪分析单个核细胞，然后与构象特异的P53抗体孵育，该抗体识别未折叠的P53三级结构。AD患者的单个核细胞表达突变型P53的量高于非AD患者，这支持了构象突变P53作为区分AD和非AD患者的新标志物的研究。我们还观察到P53的表达与患者的年龄呈显著正相关。P53的表达与病程长短和简易精神状态检查值无关。
The identification of biological markers of Alzheimer's disease ( AD) can be extremely useful to improve diagnostic accuracy and/or to monitor the efficacy of putative therapies. In this regard, peripheral cells may be of great importance, because of their easy accessibility. After subjects were grouped according to diagnosis, the expression of conformationally mutant p53 in blood cells was compared by immunoprecipitation or by a cytofluorimetric assay. In total, 104 patients with AD, 92 age-matched controls, 15 patients with Parkinson's disease and 9 with other types of dementia were analyzed. Two independent methods to evaluate the differential expression of a conformational mutant p53 were developed. Mononuclear cells were analyzed by immunoprecipitation or by flow-cytometric analysis, following incubation with a conformation-specific p53 antibody, which discriminates unfolded p53 tertiary structure. Mononuclear cells from AD patients express a higher amount of mutant-like p53 compared to non-AD subjects, thus supporting the study of conformational mutant p53 as a new putative marker to discriminate AD from non-AD patients. We also observed a strong positive correlation between the expression of p53 and the age of patients. The expression of p53 was independent from the length of illness and from the Mini Mental State Examination value.