The repair of complex neuronal circuitry by transplanted and endogenous precursors.
The repair of complex neuronal circuitry by transplanted and endogenous precursors.
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DOI：
10.1602/neurorx.1.4.452
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发表时间：
2004-10-01
期刊：
影响因子：
--
通讯作者：
Macklis, Jeffrey D
中科院分区：
文献类型：
--
作者：
Emsley, Jason G;Mitchell, Bartley D;Macklis, Jeffrey D
在过去的三十年里，探索潜在的神经元替代疗法的研究集中在通过将细胞或组织移植到大脑的患病区域来替代丢失的神经元。然而，在过去的十年中，新方法的发展导致了新研究的爆炸，表明神经发生，新神经元的诞生，通常发生在成年哺乳动物大脑的两个有限和特定的区域，并且在成年哺乳动物大脑的许多部分中存在大量的多能神经前体。我们对神经发育和可塑性相关事件的理解的最新进展，包括放射状胶质细胞在发育神经发生中的作用，以及成年大脑中存在的内源性前体被诱导产生神经元和部分重新填充受神经退行性过程影响的大脑区域的能力，导致了关于大脑如何发育的观点的根本变化，以及移植或内源性前体可用于修复成人脑的方法。例如，可以以区域特异性、层特异性和神经元类型特异性的方式诱导新神经元的募集，并且在某些情况下，新募集的神经元可以与适当的靶形成长距离连接。相关分子控制的阐明可能既允许对移植前体细胞的控制，又可能允许开发用于神经退行性疾病和其他可能不需要移植外源性细胞的CNS损伤的神经元替代疗法。
During the past three decades, research exploring potential neuronal replacement therapies has focused on replacing lost neurons by transplanting cells or grafting tissue into diseased regions of the brain. However, in the last decade, the development of novel approaches has resulted in an explosion of new research showing that neurogenesis, the birth of new neurons, normally occurs in two limited and specific regions of the adult mammalian brain, and that there are significant numbers of multipotent neural precursors in many parts of the adult mammalian brain. Recent advances in our understanding of related events of neural development and plasticity, including the role of radial glia in developmental neurogenesis, and the ability of endogenous precursors present in the adult brain to be induced to produce neurons and partially repopulate brain regions affected by neurodegenerative processes, have led to fundamental changes in the views about how the brain develops, as well as to approaches by which transplanted or endogenous precursors might be used to repair the adult brain. For example, recruitment of new neurons can be induced in a region-specific, layer-specific, and neuronal type-specific manner, and, in some cases, newly recruited neurons can form long-distance connections to appropriate targets. Elucidation of the relevant molecular controls may both allow control over transplanted precursor cells and potentially allow for the development of neuronal replacement therapies for neurodegenerative disease and other CNS injuries that might not require transplantation of exogenous cells.