中国神经再生研究(英文版) ›› 2015, Vol. 10 ›› Issue (8): 1214-1215.doi: 10.4103/1673-5374.162697

• 观点:神经损伤修复保护与再生 • 上一篇    下一篇

分形趋化因子:多种策略抵消脑实质兴奋毒性损伤并引导神经保护作用

  

  • 收稿日期:2015-05-15 出版日期:2015-08-24 发布日期:2015-08-24

Fractalkine: multiple strategies to counteract glutamate receptors activation leading to neuroprotection

Clotilde Lauro   

  1. Department of Physiology and Pharmacology, Istituto Pasteur Fondazione Cenci Bolognetti, Sapienza University of Rome, 00185 Rome, Italy
  • Received:2015-05-15 Online:2015-08-24 Published:2015-08-24
  • Contact: Clotilde Lauro, Ph.D., clotilde.lauro@uniroma1.it.

摘要:

谷氨酸是大脑中主要的兴奋性氨基酸,在许多神经生理功能中发挥着关键作用。然而,过量和长期暴露于谷氨酸决定着谷氨酸受体与细胞钙之间的平衡,并会导致细胞内途径失调,进而造成神经功能障碍甚至死亡,这一过程被称为兴奋性毒性的过度激活。在过去的二十年中,兴奋毒性机制已经被认为可以用来解释神经退行性中的神经元细胞死亡特征,如亨廷顿氏,阿尔茨海默并和帕金森病,包括增加细胞内Ca 2+,氧化自由基聚集,线粒体功能障碍,并激活细胞凋亡和自噬程序。兴奋性毒性牵涉到多种神经病理症状,它代表了神经退行性疾病的共同致病途径,却具有不同的遗传病因,它在确定组织损伤程度上或许是十分重要的。而在尝试消除兴奋毒性损伤时,损伤神经元通过释放可能被周围细胞诱导的被感测可溶性因子而产生广泛细胞响应,并引导神经保护作用和组织损伤修复。在这些因素中分形趋化因子,趋化因子组成型表达被上调并在兴奋性毒性损伤下释放神经元膜。

Abstract:

Glutamate (Glu) is the main excitatory amino acid in the brain and plays a pivotal role in many neurophysiological functions. Nevertheless, an excess and prolonged exposure to Glu determines the overactivation of glutamate receptors (GluRs) with consequent impairment of cellular calcium (Ca2+) homeostasis, leading to the dysregulation of intracellular pathways and resulting in neuronal dysfunction and death, a process called excitotoxicity. In the last two decades, excitotox mechanisms have been proposed to explain the neuronal cell death characteristic of neurodegenerative diseases such as Huntington’s, Alzheimer’s and Parkinson’s disease, including increase of intracellular Ca2+, accumulation of oxidizing free radicals, impairment of mitochondrial function and activation of apoptotic and autophagic programs. Since excitotoxicity is implicated in a variety of neuropathological conditions it represents a common pathogenic pathway for neurodegenerative diseases with distinct genetic etiologies and it appears to be important in determining the extent of tissue damage.
Dr. Clotilde Lauro (Sapienza University of Rome, Italy) showed that in the attempt to counteract excitotoxic insult, damaged neurons respond by releasing soluble factors that might be sensed by surrounding cells to induce a wide range of cellular responses leading to neuroprotection and tissue damage repair. Among these factors there is fractalkine (CX3CL1), a chemokine constitutively expressed on neuronal membrane that is upregulated, cleaved and released upon excitotoxic insult.