TGF-β and the regulation of neuron survival and death
TGF-β and the regulation of neuron survival and death
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DOI：
10.1016/s0928-4257(01)00077-8
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发表时间：
2002-01-01
影响因子：
--
通讯作者：
Unsicker, K
中科院分区：
文献类型：
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作者：
Krieglstein, K;Strelau, J;Unsicker, K
转化生长因子-β（TGF-β）构成多功能细胞因子的超家族，在形态发生、细胞分化和组织重塑中具有重要意义。在发育中的神经系统中，TGF-β 2和-β 3出现在放射状和星形胶质细胞以及许多有丝分裂后分化的神经元群体中。TGF-β 1仅限于脉络丛和脑膜。除了与神经胶质细胞成熟和性能相关的功能外，TGF-β 2和TGF-β 3是神经元存活的重要调节剂。与神经营养因子（例如神经营养因子）相反，TGF-β本身最可能不是神经营养因子。然而，它们可以显着增加选择神经营养因子的效力。成纤维细胞生长因子-2、睫状神经营养因子和胶质细胞系衍生的神经营养因子（GDNF）。在GDNF的情况下，我们已经表明，GDNF不能促进高度纯化的神经元群体在体外的生存，除非它补充了TGF-β。这也适用于体内情况，其中所有三种TGF-β同种型的抗体完全阻止GDNF对轴突切断的靶剥夺神经元的营养作用。除了TGF-β同种型-β 2和-β 3之外，TGF-β超家族的其他成员在神经系统中表达，在胚胎图案形成、细胞迁移和神经递质确定中具有重要作用。我们克隆并表达了一种新的TGF-β，命名为生长/分化因子-15（GDF-15）。GDF-15在脉络丛中合成并释放到CSF中，但也发生在发育和成人大脑的所有研究区域中。GDF-15在体外和体内是发育和6-OHDA损伤的中脑多巴胺能神经元的有效营养因子，与GDNF的效力相匹配。(C)2002爱思唯尔科技有限公司。保留所有权利。
Transforming growth factor-betas (TGF-betas) constitute a superfamily of multifunctional cytokines with important implications in morphogenesis, cell differentiation, and tissue remodeling. In the developing nervous system, TGF-beta2 and -beta3 occur in radial and astroglial cells as well as in many populations of postmitotic, differentiating neurons. TGF-beta1 is restricted to the choroid plexus and meninges. In addition to functions related to glial cell maturation and performances, TGF-beta2 and -beta3 are important regulators of neuron survival. In contrast to neurotrophic factors, as for example, neurotrophins, TGF-betas are most likely not neurotrophic by themselves. However, they can dramatically increase the potency of select neurotrophins. fibroblast growth factor-2, ciliary neurotrophic factor, and glial cell line-derived neurotrophic factor (GDNF). In the case of GDNF, we have shown that GDNF fails to promote the survival of highly purified neuron populations in vitro unless it is supplemented with TGF-beta. This also applies to the in vivo situation, where antibodies to all three TGF-beta isoforms fully prevent the trophic effect of GDNF on axotomized, target-deprived neurons. In addition to the TGF-beta isoforms -beta2 and -beta3, other members of the TGF-beta superfamily are expressed in the nervous system having important roles in embryonic patterning, cell migration, and neuronal transmitter determination. We have cloned and expressed a novel TGF-beta, named growth/differentiation factor-15 (GDF-15). GDF-15 is synthesized in the choroid plexus and released into the CSF, but also occurs in all regions investigated of the developing and adult brain. GDF-15 is a potent trophic factor for developing and 6-OHDA-lesioned midbrain dopaminergic neurons in vitro and in vivo, matching the potency of GDNF. (C) 2002 Elsevier Science Ltd. All rights reserved.