Greber S, Lubec G, Cairns N, Fountoulakis M
University of Vienna, Department of Pediatrics, Austria.
Electrophoresis. 1999 Apr-May;20(4-5):928-34. doi: 10.1002/(SICI)1522-2683(19990101)20:4/5<928::AID-ELPS928>3.0.CO;2-Z.
Synaptosomal associated protein 25 kDa (snap-25) is a widely distributed membrane-associated protein in the brain, mainly localized in nerve terminals. In nerve terminals, snap-25 participates in docking and/or fusion of synaptic vesicles with the plasmalemma, a process essential for synaptic vesicle exocytosis. Recent work suggests a role in brain development, forming presynaptic sites by regulating axonal outgrowth and nerve growth-induced neurite elongation. In Down syndrome (DS) brain, it is abnormally developed from early life, and brain pathology becomes even more pronounced when Alzheimer's disease (AD) develops in the fourth decade. This information led us to examine snap-25 in the brain of patients with DS and AD. We studied snap-25 and glial fibrillary acidic protein (GFAP) brain levels in five individual brain areas of 9 aged patients with DS, 9 patients with AD and 9 controls, applying two-dimensional gel electrophoresis. Decreased snap-25 levels were found in the five brain regions of the patients with DS and AD. Increased expression levels of GFAP were found in the frontal, parietal, temporal and occipital cortex regions of the DS and AD patients. Decreased snap-25 protein levels in the brain of DS and AD may reflect impaired synaptogenesis or represent neuronal loss. Findings of increased GFAP, a marker for neuronal loss, along with data from literature would support the notion of decreased snap-25 secondary to neuronal decay in both neurodegenerative disorders.
突触体相关蛋白25千道尔顿（snap-25）是一种在大脑中广泛分布的膜相关蛋白，主要定位于神经末梢。在神经末梢中，snap-25参与突触小泡与质膜的对接和/或融合，这是突触小泡胞吐作用所必需的过程。最近的研究表明，它在大脑发育中发挥作用，通过调节轴突生长和神经生长诱导的神经突伸长来形成突触前位点。在唐氏综合征（DS）患者的大脑中，从早期就发育异常，当在第四个十年患阿尔茨海默病（AD）时，脑部病变会更加明显。这些信息促使我们研究DS和AD患者大脑中的snap-25。我们应用二维凝胶电泳技术，研究了9名老年DS患者、9名AD患者和9名对照者五个脑区中snap-25和胶质纤维酸性蛋白（GFAP）的脑水平。在DS和AD患者的五个脑区中发现snap-25水平降低。在DS和AD患者的额叶、顶叶、颞叶和枕叶皮质区域发现GFAP表达水平升高。DS和AD患者大脑中snap-25蛋白水平降低可能反映突触发生受损或代表神经元丢失。GFAP是神经元丢失的标志物，其升高的结果以及文献数据将支持这样的观点，即在这两种神经退行性疾病中，snap-25的降低继发于神经元衰退。
