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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Secreted proNGF is a pathophysiological death-inducing ligand after adult CNS injury
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Secreted proNGF is a pathophysiological death-inducing ligand after adult CNS injury

机译：成人中枢神经系统损伤后分泌的proNGF是一种病理生理死亡诱导配体

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摘要

The unprocessed precursor of the neurotrophin nerve growth factor (NGF), proNGF, has been suggested to be a death-inducing ligand for the neurotrophin receptor p75. Whether proNGF is a true pathophysiological ligand that is secreted, binds p75, and activates cell death in vivo, however, has remained unknown. Here, we report that after brain injury, proNGF was induced and secreted in an active form capable of triggering apoptosis in culture. We further demonstrate that proNGF binds p7S in vivo and that disruption of this binding results in complete rescue of injured adult corticospinal neurons. These data together suggest that proNGF binding to p75 is responsible for the death of adult corticospinal neurons after lesion, and they help to establish proNGF as the pathophysiological ligand that activates the cell-death program by means of p75 after brain injury. Interference in the binding of proNGF to p75 may provide a therapeutic approach for the treatment of disorders involving neuronal loss.
机译：神经营养蛋白神经生长因子（NGF）的未加工前体proNGF被认为是神经营养蛋白受体p75的死亡诱导配体。 proNGF是否是一种真正的病理生理配体，在体内是否分泌，结合p75并激活细胞死亡，这一点仍然未知。在这里，我们报道脑损伤后，proNGF被诱导并以能够触发文化中细胞凋亡的活性形式被分泌。我们进一步证明proNGF在体内结合p7S，并且这种结合的破坏导致受伤的成年皮质脊髓神经元的完全抢救。这些数据共同表明，proNGF与p75的结合是造成损伤后成人皮质脊髓神经元死亡的原因，并且它们有助于建立proNGF作为在脑损伤后通过p75激活细胞死亡程序的病理生理配体。 proNGF与p75结合的干扰可能为治疗涉及神经元丢失的疾病提供治疗方法。

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