Aliperti Vincenza, Donizetti Aldo
Department of Biology, University of Naples Federico II Naples, Italy.
Front Mol Neurosci. 2016 Mar 2;9:15. doi: 10.3389/fnmol.2016.00015. eCollection 2016.
Brain-derived neurotrophic factor (BDNF) is a neurotrophin family member that is highly expressed and widely distributed in the brain. BDNF is critical for neural survival and plasticity both during development and in adulthood, and dysfunction in its signaling may contribute to a number of neurodegenerative disorders. Deep understanding of the BDNF-activated molecular cascade may thus help to find new biomarkers and therapeutic targets. One interesting direction is related to the early phase of BDNF-dependent gene expression regulation, which is responsible for the activation of selective gene programs that lead to stable functional and structural remodeling of neurons. Immediate-early coding genes activated by BDNF are under investigation, but the involvement of the non-coding RNAs is largely unexplored, especially the long non-coding RNAs (lncRNAs). lncRNAs are emerging as key regulators that can orchestrate different aspects of nervous system development, homeostasis, and plasticity, making them attractive candidate markers and therapeutic targets for brain diseases. We used microarray technology to identify differentially expressed lncRNAs in the immediate response phase of BDNF stimulation in a neuronal cell model. Our observations on the putative functional role of lncRNAs provide clues to their involvement as master regulators of gene expression cascade triggered by BDNF.
脑源性神经营养因子（BDNF）是神经营养因子家族成员，在大脑中高表达且分布广泛。BDNF在发育过程和成年期对神经存活和可塑性至关重要，其信号传导功能障碍可能导致多种神经退行性疾病。因此，深入了解BDNF激活的分子级联反应可能有助于找到新的生物标志物和治疗靶点。一个有趣的方向与BDNF依赖的基因表达调控的早期阶段有关，该阶段负责激活选择性基因程序，从而导致神经元进行稳定的功能和结构重塑。BDNF激活的即刻早期编码基因正在研究中，但非编码RNA的作用在很大程度上尚未被探索，尤其是长链非编码RNA（lncRNA）。lncRNA正成为关键调节因子，可协调神经系统发育、稳态和可塑性的不同方面，使其成为脑部疾病有吸引力的候选标志物和治疗靶点。我们使用微阵列技术在神经元细胞模型中鉴定BDNF刺激即刻反应阶段差异表达的lncRNA。我们对lncRNA假定功能作用的观察为它们作为BDNF触发的基因表达级联反应的主要调节因子的参与提供了线索。
