TGF-beta and the regulation of neuron survival and death.
TGF-beta and the regulation of neuron survival and death.
复制标题
TGF-β 与神经元存活和死亡的调节。
DOI：
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发表时间：
2002
期刊：
影响因子：
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通讯作者：
K. Unsicker
中科院分区：
文献类型：
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作者：
K. Krieglstein;J. Strelau;A. Schober;A. Sullivan;K. Unsicker
转化生长因子-β是一个多功能细胞因子超家族，在形态发生、细胞分化和组织重塑等方面具有重要意义。在发育中的神经系统中，转化生长因子-β2和-β3存在于放射状细胞和星形胶质细胞以及许多有丝分裂后、分化的神经元中。转化生长因子-β1仅限于脉络丛和脑膜。除了与胶质细胞成熟和功能相关的功能外，转化生长因子-β2和-β3也是神经元存活的重要调节因子。与神经营养因子相反，例如神经营养因子，转化生长因子-β很可能本身并不具有神经营养作用。然而，它们可以显著提高选择性神经营养因子、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神经营养因子(GDNF)的效力。在GDNF的情况下，我们已经证明GDNF在体外不能促进高纯度神经元群体的存活，除非它补充转化生长因子-β。这也适用于体内的情况，其中所有三种转化生长因子-β亚型的抗体完全阻止了GDNF对轴突切除的、靶标剥夺的神经元的营养作用。除了转化生长因子-β2和转化生长因子-β3亚型外，转化生长因子-β超家族的其他成员在神经系统中表达，在胚胎发育、细胞迁移和神经递质测定中发挥重要作用。我们克隆并表达了一种新的转化生长因子-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脑脊液中，但也存在于发育中和成人大脑的所有区域。GDF-15是一种有效的营养因子，在体外和体内对发育和6-OHDA缺失的中脑多巴胺能神经元具有与GDNF相匹配的作用。
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.