Miranda E, Lomas D A
Department of Medicine, University of Cambridge, Cambridge Institute for Medical Research, Wellcome Trust/Medical Research Council Building, Hills Road, Cambridge CB2 2XY, United Kingdom.
Cell Mol Life Sci. 2006 Mar;63(6):709-22. doi: 10.1007/s00018-005-5077-4.
Proteinases and their inhibitors play important roles in neural development, homeostasis and disease. Neuroserpin is a member of the serine proteinase inhibitor (serpin) superfamily that is secreted from the growth cones of neurons and inhibits the enzyme tissue-type plasminogen activator (tPA). The temporal and spatial pattern of neuroserpin expression suggests a role in synaptogenesis and is most prominent in areas of the brain that participate in learning, memory and behaviour. Neuroserpin also provides neuronal protection in pathologies such as cerebral ischaemia and epilepsy by preventing excessive activity of tPA. Point mutations in neuroserpin cause aberrant conformational transitions and the formation of loop-sheet polymers that are retained within the endoplasmic reticulum of neurons, forming inclusion bodies that underlie an autosomal dominant dementia that we have called familial encephalopathy with neuroserpin inclusion bodies or FENIB. We review here the role of neuroserpin and other proteinase inhibitors in brain development, function and disease.
蛋白酶及其抑制剂在神经发育、体内平衡和疾病中发挥着重要作用。神经丝氨酸蛋白酶抑制剂是丝氨酸蛋白酶抑制剂（serpin）超家族的成员，由神经元的生长锥分泌，可抑制组织型纤溶酶原激活剂（tPA）。神经丝氨酸蛋白酶抑制剂的时空表达模式表明其在突触形成中起作用，并且在参与学习、记忆和行为的脑区最为显著。神经丝氨酸蛋白酶抑制剂还通过防止tPA的过度活性在诸如脑缺血和癫痫等病理状态下提供神经保护。神经丝氨酸蛋白酶抑制剂中的点突变会导致异常的构象转变和环片聚合物的形成，这些聚合物保留在神经元的内质网中，形成包涵体，这是一种常染色体显性痴呆的基础，我们称之为伴有神经丝氨酸蛋白酶抑制剂包涵体的家族性脑病（FENIB）。我们在此综述神经丝氨酸蛋白酶抑制剂和其他蛋白酶抑制剂在脑发育、功能和疾病中的作用。
