Okita Kenji, Matsukawa Noriyuki, Maki Mina, Nakazawa Hideka, Katada Eiichi, Hattori Manabu, Akatsu Hiroyasu, Borlongan Cesario V, Ojika Kosei
Department of Neurology and Neuroscience, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Aichi 467-8601, Japan.
Biochem Biophys Res Commun. 2009 Feb 6;379(2):272-6. doi: 10.1016/j.bbrc.2008.12.037. Epub 2008 Dec 25.
Hippocampal cholinergic neurostimulating peptide (HCNP), which enhances acetylcholine synthesis and induces cholinergic phenotype development of the septohippocampal system, is derived from HCNP precursor protein (HCNPpp), also known as phosphatidylethanolamine binding protein (PEBP) and Raf kinase inhibitor protein (RKIP). Our previous study demonstrated that expression of HCNPpp mRNA was decreased in the hippocampi of autopsied brains of Alzheimer's disease (AD) patients, indicating the association of HCNP with the pathogenesis of AD. To clarify the involvement of gene variations in the promoter region of the gene encoding HCNPpp in this mRNA reduction, we analyzed DNA polymorphisms or mutations within this gene promoter region in AD patients by direct sequencing. The promoter was found to contain a CpG island without a TATA box, an element of housekeeping gene promoters. Moreover, no disease-specific polymorphisms or mutations were identified, suggesting that the decrease of mRNA can be ascribed to transcriptional or posttranscriptional changes in activity.
海马胆碱能神经刺激肽（HCNP）可增强乙酰胆碱的合成，并诱导海马隔区系统胆碱能表型的发育，它源自HCNP前体蛋白（HCNPpp），该蛋白也被称为磷脂酰乙醇胺结合蛋白（PEBP）和Raf激酶抑制蛋白（RKIP）。我们之前的研究表明，在阿尔茨海默病（AD）患者尸检大脑的海马体中，HCNPpp mRNA的表达降低，这表明HCNP与AD的发病机制有关。为了阐明编码HCNPpp的基因启动子区域的基因变异与这种mRNA减少之间的关系，我们通过直接测序分析了AD患者该基因启动子区域内的DNA多态性或突变。发现该启动子包含一个没有TATA盒的CpG岛，这是管家基因启动子的一个元件。此外，未发现疾病特异性的多态性或突变，这表明mRNA的减少可归因于转录或转录后活性的变化。
