Maki Mina, Matsukawa Noriyuki, Yuasa Hiroyuki, Otsuka Yasushi, Yamamoto Takayuki, Akatsu Hiroyasu, Okamoto Takashi, Ueda Ryuzo, Ojika Kosei
Second Department of Internal Medicine, Medical School, Nagoya City University, Japan.
J Neuropathol Exp Neurol. 2002 Feb;61(2):176-85. doi: 10.1093/jnen/61.2.176.
Hippocampal cholinergic neurostimulating peptide (HCNP) is involved in the phenotype development of the septo-hippocampal system. HCNP precursor protein (HCNP-pp) is known to interact with other molecules including phosphatidylethanolamine and Raf-1 kinase, and is also known as phosphatidylethanolamine-binding protein and raf kinase-inhibitory protein. To assess whether HCNP-pp is involved in the pathogenesis of Alzheimer disease (AD), the expression levels of its mRNA in the hippocampus of autopsy brains from patients with dementia (including AD and ischemic vascular dementia) were compared with those of non-demented control subjects. The in situ hybridization analysis revealed that the expression of HCNP-pp mRNA in patients with clinically late-onset AD was decreased in the hippocampal CA1 field, but not in the CA3 field or the dentate gyrus. The early-onset AD patients showed a wide range of expression levels in the hippocampal sub-regions. Northern blot analysis of HCNP-pp mRNA in brain tissue supported these observations. Since HCNP is known to stimulate the enzymatic activity of choline acetyltransferase in neurons, its low expression in the CAI field of AD patients may explain the downregulation of cholinergic neurons seen in these patients and may thus contribute to the pathogenic processes underlying AD.
海马胆碱能神经刺激肽（HCNP）参与隔海马系统的表型发育。已知HCNP前体蛋白（HCNP-pp）可与包括磷脂酰乙醇胺和Raf-1激酶在内的其他分子相互作用，并且也被称为磷脂酰乙醇胺结合蛋白和raf激酶抑制蛋白。为了评估HCNP-pp是否参与阿尔茨海默病（AD）的发病机制，将痴呆患者（包括AD和缺血性血管性痴呆）尸检脑海马中其mRNA的表达水平与非痴呆对照受试者的进行比较。原位杂交分析显示，临床晚发型AD患者海马CA1区HCNP-pp mRNA的表达降低，但CA3区和齿状回未降低。早发型AD患者在海马亚区表现出广泛的表达水平。脑组织中HCNP-pp mRNA的Northern印迹分析支持了这些观察结果。由于已知HCNP可刺激神经元中胆碱乙酰转移酶的酶活性，其在AD患者CAI区的低表达可能解释了这些患者中胆碱能神经元的下调，因此可能有助于AD的发病过程。
