California Institute for Quantitative Biosciences, University of California at Berkeley, Berkeley, CA 94720, USA.
Department of Chemical and Biomolecular Engineering, University of California at Berkeley, Berkeley, CA 94720, USA.
Cell Tissue Res. 2018 Jan;371(1):115-124. doi: 10.1007/s00441-017-2709-6. Epub 2017 Nov 10.
The genesis of new neurons from neural stem cells in the adult brain offers the hope that this mechanism of plasticity can be harnessed for the treatment of brain injuries and diseases. However, neurogenesis becomes impaired during the normal course of aging; this is also the primary risk factor for most neurodegenerative diseases. The local microenvironment that regulates the function of resident neural stem cells (the "neurogenic niche") is a particularly complex network of various signaling mechanisms, rendering it especially challenging for the dissection of the control of these cells but offering the potential for the advancement of our understanding of the regulation/misregulation of neurogenesis. In this review, we examine the factors that control neurogenesis in an age-dependent manner, and we define these signals by the extrinsic mechanism through which they are presented to the neural stem cells. Secreted signals, cell-contact-dependent signals, and extracellular matrix cues all contribute to the regulation of the aging neurogenic niche and offer points of therapeutic intervention.
成年大脑中的神经干细胞产生新神经元，为利用这种可塑性机制治疗脑损伤和疾病带来了希望。然而，神经发生在正常衰老过程中受到损害；这也是大多数神经退行性疾病的主要风险因素。调节常驻神经干细胞功能的局部微环境（“神经发生龛”）是一个特别复杂的各种信号机制网络，这使得对这些细胞的控制进行剖析特别具有挑战性，但为我们深入了解神经发生的调节/失调提供了潜力。在这篇综述中，我们检查了以年龄依赖性方式控制神经发生的因素，并通过它们呈现给神经干细胞的外在机制来定义这些信号。分泌信号、细胞接触依赖性信号和细胞外基质线索都有助于调节衰老的神经发生龛，并提供治疗干预的切入点。
