CLN3 defines a novel antiapoptotic pathway operative in neurodegeneration and mediated by ceramide
CLN3 defines a novel antiapoptotic pathway operative in neurodegeneration and mediated by ceramide
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DOI：
10.1006/mgme.1999.2834
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发表时间：
1999-04-01
影响因子：
3.8
通讯作者：
Boustany, RM
中科院分区：
文献类型：
--
作者：
Puranam, KL;Guo, WX;Boustany, RM
青少年神经性ceroid脂褐质病或Batten病（JNCL）是一种以失明、癫痫发作、认知能力下降和早期死亡为特征的神经退行性疾病。脑萎缩和视网膜色素变性是由神经元和感光细胞凋亡引起的。JNCL中的CLN3基因缺陷编码一种新的438个氨基酸的蛋白。大多数受影响的基因都含有缺失，导致蛋白质被截断。CLN3在NT2细胞中的过表达可促进细胞生长，逆转血清饥饿诱导的生长抑制，并可保护长春新碱、星孢素和etopo苷诱导的细胞凋亡，但不能保护神经酰胺引起的死亡。CLN3调节内源性和长春新碱激活的神经酰胺，从而通过影响神经酰胺的生成来抑制细胞凋亡。(C) 1999学术出版社。
Juvenile neuronal ceroid lipofuscinosis or Batten disease (JNCL) is a neurodegenerative disorder characterized by blindness, seizures, cognitive decline and early death. Brain atrophy and retinitis pigmentosa ensue because of neuronal and photoreceptor apoptosis. The CLN3 gene defective in JNCL encodes a novel 438 amino acid protein. Most affected genes harbor a deletion resulting in a truncated protein. CLN3 overexpression in NT2 cells enhances growth, reverses growth inhibition induced by serum starvation and protects hom apoptosis induced by vincristine, staurosporine, and etoposide but not from death caused by ceramide. CLN3 modulates endogenous and vincristine-activated ceramide, and therefore suppresses apoptosis by impacting generation of ceramide. (C) 1999 Academic Press.