Crowther Damian C
University of Cambridge Neurology Unit, Cambridge Institute for Medical Research, Cambridge, UK.
Hum Mutat. 2002 Jul;20(1):1-14. doi: 10.1002/humu.10100.
Familial conformational diseases occur when a mutation alters the conformation of a protein resulting in abnormal intermolecular interactions, protein aggregation, and consequent tissue damage. The molecular mechanisms of conformational disease are best understood for the serine protease inhibitor (serpin) superfamily of proteins. The serpinopathies include alpha(1)-antitrypsin (SERPINA1) deficiency and the newly characterized familial encephalopathy with neuroserpin inclusion bodies (FENIB) resulting from mutations in the neuroserpin (SERPINI1) gene. This review discusses how insights gained from the study of the serpins may be used to guide our research into other common diseases such as Alzheimer disease, Huntington disease, and Parkinson disease.
当突变改变蛋白质的构象，导致异常的分子间相互作用、蛋白质聚集以及随之而来的组织损伤时，就会发生家族性构象疾病。对于丝氨酸蛋白酶抑制剂（serpin）超家族蛋白，构象疾病的分子机制得到了最好的理解。丝氨酸蛋白酶抑制剂病包括α1抗胰蛋白酶（SERPINA1）缺乏症以及新发现的由神经丝氨酸蛋白酶（SERPINI1）基因突变导致的伴有神经丝氨酸蛋白酶包涵体的家族性脑病（FENIB）。本综述讨论了从丝氨酸蛋白酶抑制剂研究中获得的见解如何用于指导我们对其他常见疾病的研究，如阿尔茨海默病、亨廷顿病和帕金森病。
