Bone Marrow Research Laboratories, Parkville 3050, Australia.
Expert Opin Ther Targets. 2010 Aug;14(8):869-79. doi: 10.1517/14728222.2010.501332.
Expansion and ultimately homeostasis of neural cell number is exquisitely regulated by molecular genetic networks operating in neural stem and progenitor cells (NSPCs) and in the neural stem cell niche during embryogenesis and in the adult brain. Transcription factors are crucial in orchestrating the correct cell-specific and temporal expression of all factors involved in these signalling networks. Aberrant expression of these factors can lead to abnormal brain development if this occurs during embryogenesis. In the adult brain, loss of neurogenic potential can lead to cognitive deficits and in combination with neural death can even contribute to neurodegenerative disease progress.
This review focuses on a number of recent discoveries identifying the role of the transcription factor cAMP response element binding (CREB) protein in regulating brain development and neurogenesis in the adult brain.
The significance of these discoveries is presented in the context of human brain disorders and how this knowledge could contribute to pharmacotherapeutic interventions targeting CREB signalling aimed at treating such diseases.
Unravelling these precise molecular genetic networks is crucial to understanding how neural stem and progenitor cells function.
神经干细胞和祖细胞(NSPCs)中的分子遗传网络,以及胚胎发生和成年大脑中的神经干细胞龛,在调控神经细胞数量的扩增和最终稳态方面发挥着极其重要的作用。转录因子在协调所有参与这些信号网络的因子的正确细胞特异性和时间表达方面起着至关重要的作用。如果这些因子在胚胎发生过程中异常表达,可能会导致大脑发育异常。在成年大脑中,神经发生潜能的丧失可导致认知缺陷,并且与神经死亡结合甚至可导致神经退行性疾病进展。
这篇综述集中讨论了最近的一些发现,这些发现确定了转录因子 cAMP 反应元件结合(CREB)蛋白在调节大脑发育和成年大脑中的神经发生中的作用。
这些发现的意义是在人类大脑疾病的背景下提出的,以及这些知识如何有助于针对 CREB 信号的药物治疗干预,以治疗此类疾病。
揭示这些精确的分子遗传网络对于理解神经干细胞和祖细胞的功能至关重要。