Role and Therapeutic Potential of Astrocytes in Amyotrophic Lateral Sclerosis.
Role and Therapeutic Potential of Astrocytes in Amyotrophic Lateral Sclerosis.
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DOI：
10.2174/1381612823666170622095802
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发表时间：
2017
影响因子：
3.1
通讯作者：
Vargas MR
中科院分区：
文献类型：
--
作者：
Pehar M;Harlan BA;Killoy KM;Vargas MR
肌萎缩性侧索硬化症（ALS）的特点是脊髓、脑干和运动皮层的运动神经元进行性变性。运动神经元进行性变性的分子机制尚不清楚，但涉及一个非细胞自主过程。在急性损伤或退行性疾病中，星形胶质细胞采用一种被称为星形胶质增生的反应性表型。星形胶质增生是星形胶质细胞生物学的复杂重塑，很可能代表了一系列潜在的表型，这些表型以损伤特异性的方式影响神经元的功能和存活。在ALS患者中，反应性星形胶质细胞围绕着上部和下部退化的运动神经元，并在病理中发挥关键作用。很明显，星形胶质细胞在ALS病理中起着重要作用。通过失去正常功能或获得新的特征，星形胶质细胞能够影响运动神经元的命运和疾病的进展。不同细胞培养模型的使用表明，als星形胶质细胞能够通过分泌一种可溶性因子诱导运动神经元死亡。在这里，我们讨论了几种致病机制，已提出的解释星形胶质细胞介导的运动神经元死亡的ALS。此外，本文还回顾了恢复星形胶质细胞介导的运动神经元毒性的策略实例，以说明星形胶质细胞在ALS中的治疗潜力。由于星形胶质细胞在ALS病理中发挥的核心作用，旨在调节星形胶质细胞生物学的治疗可能有助于开发阻止ALS进展的整体治疗方法。
Amyotrophic lateral sclerosis (ALS) is characterized by the progressive degeneration of motor neurons in the spinal cord, brain stem, and motor cortex. The molecular mechanism underlying the progressive degeneration of motor neuron remains uncertain but involves a non-cell autonomous process. In acute injury or degenerative diseases astrocytes adopt a reactive phenotype known as astrogliosis. Astrogliosis is a complex remodeling of astrocyte biology and most likely represents a continuum of potential phenotypes that affect neuronal function and survival in an injury-specific manner. In ALS patients, reactive astrocytes surround both upper and lower degenerating motor neurons and play a key role in the pathology. It has become clear that astrocytes play a major role in ALS pathology. Through loss of normal function or acquired new characteristics, astrocytes are able to influence motor neuron fate and the progression of the disease. The use of different cell culture models indicates that ALS-astrocytes are able to induce motor neuron death by secreting a soluble factor(s). Here, we discuss several pathogenic mechanisms that have been proposed to explain astrocyte-mediated motor neuron death in ALS. In addition, examples of strategies that revert astrocyte-mediated motor neuron toxicity are reviewed to illustrate the therapeutic potential of astrocytes in ALS. Due to the central role played by astrocytes in ALS pathology, therapies aimed at modulating astrocyte biology may contribute to the development of integral therapeutic approaches to halt ALS progression.
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影响因子：
6.2
作者：
Almad AA;Doreswamy A;Gross SK;Richard JP;Huo Y;Haughey N;Maragakis NJ
通讯作者：
Maragakis NJ
影响因子：
16.6
作者：
Arthur KC;Calvo A;Price TR;Geiger JT;Chiò A;Traynor BJ
通讯作者：
Traynor BJ
影响因子：
9.3
作者：
Bracchi-Ricard V;Lambertsen KL;Ricard J;Nathanson L;Karmally S;Johnstone J;Ellman DG;Frydel B;McTigue DM;Bethea JR
通讯作者：
Bethea JR
DOI：
10.1016/j.bbrc.2006.05.042
发表时间：
2006-07-14
影响因子：
3.1
作者：
Aksoy, Pinar;White, Thomas A.;Chini, Eduardo N.
通讯作者：
Chini, Eduardo N.
星形胶质细胞疤痕形成有助于中枢神经系统轴突再生。
影响因子：
64.8
作者：
Anderson MA;Burda JE;Ren Y;Ao Y;O'Shea TM;Kawaguchi R;Coppola G;Khakh BS;Deming TJ;Sofroniew MV
通讯作者：
Sofroniew MV