Instituto de Investigaciones Biomédicas and Center for Biomedical Research on Rare Diseases (CIBERER), Madrid, Spain.
Neurochem Int. 2011 May;58(6):613-9. doi: 10.1016/j.neuint.2011.01.019. Epub 2011 Feb 12.
Alzheimer's disease as well as prion-related encephalopathies are neurodegenerative disorders of the central nervous system, which cause mental deterioration and progressive dementia. Both pathologies appear to be primarily associated with the pathological accumulation and deposit of β-amyloid or prion peptides in the brain, and it has been even suggested that neurotoxicity induced by these peptides would be associated to essentially similar pathogenic mechanisms, in particular to those that follow the activation of microglial cells. To probe whether the neurotoxic effects induced by the β-amyloid and prion peptides are actually mediated by similar glial-associated mechanisms, we have examined the differential expression of genes in SH-SY5Y neuroblastoma cells incubated with conditioned media from β-amyloid or prion-stimulated THP-1 monocytic cells. According to microarray analysis, not many coincidences are observed and only four genes (Hint3, Psph, Daam1 and c-Jun) appear to be commonly upregulated by both peptides. Furthermore, c-Jun appears to be involved in the cell death mediated by both peptides.
阿尔茨海默病和朊病毒相关脑病是中枢神经系统的神经退行性疾病，可导致精神恶化和进行性痴呆。这两种病理学似乎主要与β-淀粉样蛋白或朊病毒肽在大脑中的病理性积累和沉积有关，甚至有人提出，这些肽诱导的神经毒性与本质上相似的致病机制有关，特别是与那些紧随小胶质细胞激活的机制有关。为了探究β-淀粉样蛋白和朊病毒肽诱导的神经毒性是否确实是通过类似的与神经胶质相关的机制介导的，我们研究了用β-淀粉样蛋白或朊病毒刺激的 THP-1 单核细胞的条件培养基孵育的 SH-SY5Y 神经母细胞瘤细胞中基因的差异表达。根据微阵列分析，观察到的一致性并不多，只有四个基因（Hint3、Psph、Daam1 和 c-Jun）似乎被两种肽共同上调。此外，c-Jun 似乎参与了这两种肽介导的细胞死亡。
