Upper and Lower Motor Neurons and the Skeletal Muscle: Implication for Amyotrophic Lateral Sclerosis (ALS).

4区 生物学 Q3 Medicine
Fiorella Colasuonno, Rachel Price, Sandra Moreno
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引用次数: 0

Abstract

The relationships between motor neurons and the skeletal muscle during development and in pathologic contexts are addressed in this Chapter.We discuss the developmental interplay of muscle and nervous tissue, through neurotrophins and the activation of differentiation and survival pathways. After a brief overview on muscular regulatory factors, we focus on the contribution of muscle to early and late neurodevelopment. Such a role seems especially intriguing in relation to the epigenetic shaping of developing motor neuron fate choices. In this context, emphasis is attributed to factors regulating energy metabolism, which may concomitantly act in muscle and neural cells, being involved in common pathways.We then review the main features of motor neuron diseases, addressing the cellular processes underlying clinical symptoms. The involvement of different muscle-associated neurotrophic factors for survival of lateral motor column neurons, innervating MyoD-dependent limb muscles, and of medial motor column neurons, innervating Myf5-dependent back musculature is discussed. Among the pathogenic mechanisms, we focus on oxidative stress, that represents a common and early trait in several neurodegenerative disorders. The role of organelles primarily involved in reactive oxygen species scavenging and, more generally, in energy metabolism-namely mitochondria and peroxisomes-is discussed in the frame of motor neuron degeneration.We finally address muscular involvement in amyotrophic lateral sclerosis (ALS), a multifactorial degenerative disorder, hallmarked by severe weight loss, caused by imbalanced lipid metabolism. Even though multiple mechanisms have been recognized to play a role in the disease, current literature generally assumes that the primum movens is neuronal degeneration and that muscle atrophy is only a consequence of such pathogenic event. However, several lines of evidence point to the muscle as primarily involved in the disease, mainly through its role in energy homeostasis. Data from different ALS mouse models strongly argue for an early mitochondrial dysfunction in muscle tissue, possibly leading to motor neuron disturbances. Detailed understanding of skeletal muscle contribution to ALS pathogenesis will likely lead to the identification of novel therapeutic strategies.

上下运动神经元和骨骼肌:对肌萎缩侧索硬化症(ALS)的影响。
本章将讨论运动神经元与骨骼肌在发育过程和病理背景下的关系。我们讨论肌肉和神经组织的发育相互作用,通过神经营养因子和分化和生存途径的激活。在对肌肉调节因子的简要概述之后,我们将重点关注肌肉对早期和晚期神经发育的贡献。这种作用在运动神经元命运选择的表观遗传塑造中似乎特别有趣。在这种情况下,重点归因于调节能量代谢的因素,这些因素可能同时作用于肌肉和神经细胞,参与共同的途径。然后,我们回顾运动神经元疾病的主要特征,解决潜在的临床症状的细胞过程。本文讨论了不同肌肉相关神经营养因子对支配myf5依赖性肢体肌肉的外侧运动柱神经元和支配myf5依赖性背部肌肉的内侧运动柱神经元存活的影响。在致病机制中,我们关注氧化应激,这代表了几种神经退行性疾病的共同和早期特征。主要参与活性氧清除的细胞器的作用,更一般地说,在能量代谢中,即线粒体和过氧化物酶体,在运动神经元变性的框架内进行了讨论。肌萎缩性侧索硬化症(ALS)是一种多因素退行性疾病,以严重体重减轻为特征,由脂质代谢不平衡引起。尽管已经认识到多种机制在该疾病中发挥作用,但目前的文献普遍认为,原始运动是神经元变性,肌肉萎缩只是这种致病事件的结果。然而,有几条线索的证据表明,肌肉主要通过其在能量平衡中的作用参与了这种疾病。来自不同ALS小鼠模型的数据强烈支持肌肉组织中早期线粒体功能障碍,可能导致运动神经元紊乱。详细了解骨骼肌对ALS发病机制的贡献将可能导致新的治疗策略的确定。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
2.00
自引率
0.00%
发文量
0
期刊介绍: "Advances in Anatomy, Embryology and Cell Biology" presents critical reviews on all topical fields of normal and experimental anatomy including cell biology. The multi-perspective presentation of morphological aspects of basic biological phenomen in the human constitutes the main focus of the series. The contributions re-evaluate the latest findings and show ways for further research.
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