Microglia centered pathogenesis in ALS: insights in cell interconnectivity.
Microglia centered pathogenesis in ALS: insights in cell interconnectivity.
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DOI：
10.3389/fncel.2014.00117
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发表时间：
2014
影响因子：
5.3
通讯作者：
Vaz AR
中科院分区：
文献类型：
--
作者：
Brites D;Vaz AR
肌萎缩侧索硬化症（ALS）是成人运动神经元（MN）变性的最常见和最具侵略性的形式。这种疾病的原因仍然未知，但一些蛋白质突变与病理过程有关。上下MN的丧失导致进行性肌肉麻痹，并最终因呼吸衰竭而死亡。虽然最初被认为源自MN的选择性丧失，但非细胞自主性疾病的致病性概念已经成为ALS中神经胶质细胞，特别是小神经胶质细胞的贡献的最前沿。最近的研究表明，小胶质细胞可能在早期阶段对MN具有保护作用。相反，活化的小胶质细胞通过分泌神经毒性因子促进和增强MN死亡，并且终末期小胶质细胞功能受损反而可能加速疾病进展。然而，导致MN变性的小胶质细胞-神经元相互作用的性质仍然难以捉摸。我们回顾了神经退行性网络在ALS病理学中的贡献，特别关注转基因SOD 1G 93 A啮齿动物（最广泛使用的模型）中获得的数据中的每种胶质细胞类型。我们进一步讨论了神经炎症和小胶质细胞表型在ALS病理调节中的不同作用。我们提供了与功能失调的细胞间通讯相关的过程的信息，并总结了神经元和星形胶质细胞，神经元和小胶质细胞之间的病理性串扰，以及致病因素的传播的研究结果。我们还强调了神经血管破坏和外泌体运输与ALS病理学的相关性。NG 2细胞，少突胶质细胞和雪旺细胞的有害和有益的影响也将进行讨论。深入了解ALS背后复杂的细胞间扰动，包括靶点识别，将加强我们开发有效治疗方法的努力，以预防或逆转这种毁灭性疾病的症状进展。
Amyotrophic lateral sclerosis (ALS) is the most common and most aggressive form of adult motor neuron (MN) degeneration. The cause of the disease is still unknown, but some protein mutations have been linked to the pathological process. Loss of upper and lower MNs results in progressive muscle paralysis and ultimately death due to respiratory failure. Although initially thought to derive from the selective loss of MNs, the pathogenic concept of non-cell-autonomous disease has come to the forefront for the contribution of glial cells in ALS, in particular microglia. Recent studies suggest that microglia may have a protective effect on MN in an early stage. Conversely, activated microglia contribute and enhance MN death by secreting neurotoxic factors, and impaired microglial function at the end-stage may instead accelerate disease progression. However, the nature of microglial–neuronal interactions that lead to MN degeneration remains elusive. We review the contribution of the neurodegenerative network in ALS pathology, with a special focus on each glial cell type from data obtained in the transgenic SOD1G93A rodents, the most widely used model. We further discuss the diverse roles of neuroinflammation and microglia phenotypes in the modulation of ALS pathology. We provide information on the processes associated with dysfunctional cell–cell communication and summarize findings on pathological cross-talk between neurons and astroglia, and neurons and microglia, as well as on the spread of pathogenic factors. We also highlight the relevance of neurovascular disruption and exosome trafficking to ALS pathology. The harmful and beneficial influences of NG2 cells, oligodendrocytes and Schwann cells will be discussed as well. Insights into the complex intercellular perturbations underlying ALS, including target identification, will enhance our efforts to develop effective therapeutic approaches for preventing or reversing symptomatic progression of this devastating disease.
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影响因子：
5.3
作者：
Bourd-Boittin K;Basset L;Bonnier D;L'helgoualc'h A;Samson M;Théret N
通讯作者：
Théret N
DOI：
10.1093/brain/awr074
发表时间：
2011-05
期刊：
Brain : a journal of neurology
影响因子：
--
作者：
Beers DR;Henkel JS;Zhao W;Wang J;Huang A;Wen S;Liao B;Appel SH
通讯作者：
Appel SH
影响因子：
5.3
作者：
Bowerman M;Vincent T;Scamps F;Perrin FE;Camu W;Raoul C
通讯作者：
Raoul C
影响因子：
9.9
作者：
Alexianu, ME;Kozovska, M;Appel, SH
通讯作者：
Appel, SH
DOI：
10.1073/pnas.92.16.7162
发表时间：
1995-08-01
影响因子：
11.1
作者：
BONFOCO, E;KRAINC, D;LIPTON, SA
通讯作者：
LIPTON, SA