Molinari Florence, Rio Marlene, Meskenaite Virginia, Encha-Razavi Férechté, Augé Joelle, Bacq Delphine, Briault Sylvain, Vekemans Michel, Munnich Arnold, Attié-Bitach Tania, Sonderegger Peter, Colleaux Laurence
Unité de Recherches sur les Handicaps Génétiques de l'Enfant, INSERM U-393, et Département de Génétique, Hôpital Necker-Enfants Malades, Paris, France.
Science. 2002 Nov 29;298(5599):1779-81. doi: 10.1126/science.1076521.
A 4-base pair deletion in the neuronal serine protease neurotrypsin gene was associated with autosomal recessive nonsyndromic mental retardation (MR). In situ hybridization experiments on human fetal brains showed that neurotrypsin was highly expressed in brain structures involved in learning and memory. Immuno-electron microscopy on adult human brain sections revealed that neurotrypsin is located in presynaptic nerve endings, particularly over the presynaptic membrane lining the synaptic cleft. These findings suggest that neurotrypsin-mediated proteolysis is required for normal synaptic function and suggest potential insights into the pathophysiological bases of mental retardation.
神经元丝氨酸蛋白酶神经胰蛋白酶基因中的一个4碱基对缺失与常染色体隐性非综合征性智力迟钝（MR）相关。对人类胎儿大脑进行的原位杂交实验表明，神经胰蛋白酶在参与学习和记忆的脑结构中高度表达。对成人大脑切片进行的免疫电子显微镜检查显示，神经胰蛋白酶位于突触前神经末梢，尤其是位于突触间隙内衬的突触前膜上。这些发现表明，神经胰蛋白酶介导的蛋白水解作用是正常突触功能所必需的，并为智力迟钝的病理生理基础提供了潜在的见解。
