Chilumuri Amrutha, Ashioti Maria, Nercessian Amanda N, Milton Nathaniel G N
Department of Human and Health Sciences, School of Life Sciences, University of Westminster, 115 New Cavendish Street, London W1W 6UW, UK.
Health Sciences Research Centre, University of Roehampton, Holybourne Avenue, London SW15 4JD, UK.
J Neurodegener Dis. 2013;2013:879710. doi: 10.1155/2013/879710. Epub 2013 May 16.
The pons region of the Alzheimer's disease (AD) brain is one of the last to show amyloid-β (Aβ) deposits and has been suggested to contain neuroprotective compounds. Kisspeptin (KP) is a hormone that activates the hypothalamic-pituitary-gonadal axis and has been suggested to be neuroprotective against Aβ toxicity. The localization of KP, plus the established endogenous neuroprotective compounds corticotropin releasing hormone (CRH) and catalase, in tissue sections from the pons region of a male AD subject has been determined in relation to Aβ deposits. Results showed Aβ deposits also stained with KP, CRH, and catalase antibodies. At high magnification the staining of deposits was either KP or catalase positive, and there was only a limited area of the deposits with KP-catalase colocalization. The CRH does not bind Aβ, whilst both KP and catalase can bind Aβ, suggesting that colocalization in Aβ deposits is not restricted to compounds that directly bind Aβ. The neuroprotective actions of KP, CRH, and catalase were confirmed in vitro, and fibrillar Aβ preparations were shown to stimulate the release of KP in vitro. In conclusion, neuroprotective KP, CRH, and catalase all colocalize with Aβ plaque-like deposits in the pons region from a male AD subject.
阿尔茨海默病（AD）患者大脑的脑桥区域是最后出现淀粉样β蛋白（Aβ）沉积的区域之一，并且有人提出该区域含有神经保护化合物。 kisspeptin（KP）是一种激活下丘脑 - 垂体 - 性腺轴的激素，有人认为它对Aβ毒性具有神经保护作用。已确定男性AD患者脑桥区域组织切片中KP以及已确定的内源性神经保护化合物促肾上腺皮质激素释放激素（CRH）和过氧化氢酶与Aβ沉积的定位关系。结果显示，Aβ沉积物也与KP、CRH和过氧化氢酶抗体发生染色反应。在高倍放大下，沉积物的染色要么是KP阳性，要么是过氧化氢酶阳性，并且只有有限区域的沉积物存在KP - 过氧化氢酶共定位。CRH不与Aβ结合，而KP和过氧化氢酶都能与Aβ结合，这表明Aβ沉积物中的共定位并不局限于直接与Aβ结合的化合物。KP、CRH和过氧化氢酶的神经保护作用在体外得到证实，并且纤维状Aβ制剂在体外显示能刺激KP的释放。总之，神经保护物质KP、CRH和过氧化氢酶都与男性AD患者脑桥区域的Aβ斑块样沉积物共定位。
