McCall Todd, Chin Steven S, Salzman Karen L, Fults Daniel W
Department of Neurosurgery, University of Utah School of Medicine, Salt Lake City, Utah 84132-2303, USA.
Neurosurg Focus. 2006 Jan 15;20(1):E3. doi: 10.3171/foc.2006.20.1.4.
Tuberous sclerosis (TS) is a congenital neurocutaneous syndrome (or phacomatosis) characterized by widespread development of hamartomas in multiple organs. For affected individuals, neurological and psychiatric complications are the most disabling and lethal features. Although the clinical phenotype of TS is complex, only three lesions characterize the neuropathological features of the disease: cortical tubers, subependymal nodules, and subependymal giant cell astrocytomas. The latter is a benign brain tumor of mixed neuronal and glial origin. Tuberous sclerosis is caused by loss-of-function mutations in one of two genes, TSC1 or TSC2. The normal cellular proteins encoded by these genes, hamartin and tuberin, respectively, form a heterodimer that suppresses cell growth in the central nervous system by dampening the phosphatidylinositol 3-kinase signal transduction pathway. The authors review the clinical and neuropathological features of TS as well as recent research into the molecular biology of this disease. Through this work, investigators are beginning to resolve the paradoxical findings that malignant cancers seldom arise in patients with TS, even though the signaling molecules involved are key mediators of cancer cell growth.
结节性硬化症（TS）是一种先天性神经皮肤综合征（或错构瘤病），其特征是多个器官广泛出现错构瘤。对于受影响的个体而言，神经和精神并发症是最具致残性和致命性的特征。尽管TS的临床表型复杂，但只有三种病变可表征该疾病的神经病理学特征：皮质结节、室管膜下结节和室管膜下巨细胞星形细胞瘤。后者是一种起源于神经元和神经胶质细胞的混合性良性脑肿瘤。结节性硬化症由TSC1或TSC2这两个基因之一的功能丧失性突变引起。这些基因分别编码的正常细胞蛋白，即错构瘤蛋白和结节蛋白，形成一种异二聚体，通过抑制磷脂酰肌醇3激酶信号转导途径来抑制中枢神经系统中的细胞生长。作者回顾了TS的临床和神经病理学特征以及对该疾病分子生物学的最新研究。通过这项工作，研究人员开始解决一些矛盾的发现，即TS患者很少发生恶性肿瘤，尽管所涉及的信号分子是癌细胞生长的关键介质。
