中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2015, Vol. 10 ›› Issue (10): 1581-1583.doi: 10.4103/1673-5374.165269

• 观点:退行性病与再生 • 上一篇    下一篇

神经退行性疾病和神经炎症：两种病变同一目标

  

  • 收稿日期:2015-06-25 出版日期:2015-10-28 发布日期:2015-10-28
  • 基金资助:

    这一工作是由西班牙政府“卫生部”（CIBERNED：CB06/05/1104和CIBERNED基金）;“经济部和竞争力”（SAF2010-19953和SAF2013-47989-R）资助，并通过了“Generalitat加泰罗尼亚'（ALS Suport为Grups研究Consolidats2009SGR346）

Neurodegeneration and neuroinflammation: two processes, one target

Paulina Carriba*, Joan X. Comella*   

  1. Institut de Recerca de l’Hospital Universitari de la Vall d’Hebron (VHIR), Passeig Vall d’Hebron 119-129, Barcelona 08035, Spain Institut de Neurociències, Departament de Bioquímica i Biologia Molecular, Facultat de Medicina, Universitat Autònoma de Barcelona, Campus de Bellaterra (Edifici M), Bellaterra 08193, Spain; Centro de Investigación Biomèdica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona 08035, Spain
  • Received:2015-06-25 Online:2015-10-28 Published:2015-10-28
  • Contact: Paulina Carriba, Ph.D. or Joan X. Comella, Ph.D., paulina.carriba@gmail.com or joan.comella@vhir.org.
  • Supported by:

    This work was funded by the Spanish Government’s ‘Ministerio
    de Sanidad y Consumo’ (CIBERNED: CB06/05/1104 and CIBERNED grants PI2010/08 and 2013/01 to JXC); ‘Ministerio de Economía y Competitividad’ (SAF2010-19953 and SAF 2013-47989-R to JXC), and by the ‘Generalitat de Catalunya’ (Suport als Grups de Recerca Consolidats 2009SGR346). PC was awarded a ‘Beatriu de Pinos’ postdoctoral grant from the ‘Generalitat de Catalunya’ co-financed by the FP7-People-COFUND Programme. We want to thank Dra. Bruna Barneda-Zahonero for her counseling
    with epigenetics, and to Tony Horton and Clara Erice Jurecky for their comments and careful proofreading of the paper.

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摘要：

神经退行性疾病的病因是多样的，但是大多数病因都具有共同特征：错误折叠蛋白质积累，慢性及持续性神经炎症和某些细胞群体功能紊乱及死亡。最初的蛋白病变引发了神经系统中免疫防御系统激活，并且已经在一些案例中得到证明。小胶质细胞以及星形胶质细胞是中枢神经系统中涉及先天性炎症反应的主要胶质细胞。这些细胞能够探测出危险信号，并且一旦被激活就会分泌出炎性介质试图防止或阻碍损伤。然而，在一些研究中，由于小胶质细胞和星形胶质细胞间释放因子的扩大反馈会过度激活这些细胞，使炎症反应变得持久。这就促进了更多胶质细胞的聚集延长且正调节神经炎症反应并导致疾病演进，持续的神经炎症反应伴随保护机制的异常引发了神经细胞死亡。FAS凋亡抑制分子的特性表明这一神经细胞特性蛋白作为神经退行性疾病的药理目标及诊断工具具有巨大潜力。然而，必须解决如何调节FAS凋亡抑制分子表征到完全理解其如何发挥功能这样的重要问题。因为FAS凋亡抑制分子调节存活或凋亡的神经细胞对于像FasL和TNFα这样的炎性分子的反应，因此它的数量似乎就是左右神经退性结果的关键因素。就这一点而言，目前对不携带FAS凋亡抑制分子的老鼠是否会更易神经退行或是更易受神经退行性疾病的影响还尚未可知。值得注意的是，FAIM-L的修复程度可能是阻止神经细胞损伤的一种有前景的治疗方法。

Abstract:

The etiology of neurodegenerative diseases is diverse, however most of them share common characteristics: accumulation of misfolded proteins, chronic and sustained neuroinflammation, and the dysfunction and death of certain populations of neurons. The brain of Alzheimer’s disease (AD) patients presents amyloid plaques and aggregation of hyperphosphorylated Tau. The latter is also present in neurodegenerative tauopathies and in Parkinson’s disease (PD). Aggregates of ?-synuclein is the characteristic hallmark of PD. In amyotrophic lateral sclerosis (ALS), the mutation of SOD1 promotes its accumulation; and the polyglutamine expansion in huntingtin protein favors its aggregation in Huntington’s disease (HD). Thus, the initial proteinopathy could be responsible for triggering the activation of the immunological defenses in the nervous system, as it has been demonstrated in some cases. Microglia and astrocytes are the main glial cells involved in the innate inflammatory response in the central nervous system (CNS). These cells are capable of detecting danger signals, and when activated they secrete inflammatory mediators to try to protect or prevent damage. However, in some cases the inflammatory response becomes sustained by an amplified feedback of release of factors between microglia and astrocytes that further activates these cells. This promotes the recruitment of more glial cells that prolongs and up-regulates the neuroinflammatory response contributing to the progression of the disease. Neurodegeneration has a remarkable apoptotic component; sustained neuroinflammatory response along with the deregulation of protective mechanisms trigger neuronal death.