Journal of molecular neuroscience : MN
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Alzheimer disease (AD) is characterized by chronic neuroinflammation, which may lead to dysfunction in neuronal circuits. Although reactive microglia are found in association with accumulation of beta amyloid (Aβ) plaques in the AD brain, their contribution to neuronal cell loss remains speculative. A major genetic risk factor for sporadic AD is inheritance of the apolipoprotein (apo) E4 allele, which has been shown to contribute significantly to neurodegeneration in AD. ⋯ Addition of Aβ(1-40) preincubated with apoE4 to H4 cells in the presence of SNAP led to an additive IL-1β-induced COX-2 expression and PGE(2) production. These observations indicate that increased PGE(2) resulted from increased nitrosative stress, which is enhanced by apoE4. Thus a molecular understanding of the interactions of apoE4 with Aβ, NO and IL-1β on the regulation of the COX-2/prostaglandin pathway may open new avenues in understanding the mechanism of development of neurodegenerative disease such as AD.
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The objective of this study is to investigate the expression and significance of isocitrate dehydrogenase 1 (IDH1) mutation in different subtypes of human gliomas. Direct DNA sequencing, western blot, and immunohistochemistry were used to detect IDH1 mutation and IDH1 gene expression levels in 97 cases of glioma and 9 cases of other CNS tumors. IDH1 mutation was heterozygous, with wild-type arginine 132 replaced by histidine (R132H). ⋯ For example, it can be used to distinguish primary glioblastoma from secondary glioblastoma, combining TP53 mutation and loss of heterozygosity involving 1p/19q. It can also be used as a marker for some gliomas. For example, it can be used to distinguish pilocytic astrocytoma from diffuse astrocytoma, combining detected BRAF proto-oncogene mutations.