Institute of Cell Biology and Neurobiology (IBCN), National Research Council (CNR), Via del Fosso di Fiorano 64, 00143 Rome, Italy.
IRCCS Santa Lucia Foundation, Via del Fosso di Fiorano 64, 00143 Rome, Italy.
Mediators Inflamm. 2017;2017:7821672. doi: 10.1155/2017/7821672. Epub 2017 Sep 7.
The progressive and fatal loss of upper (brain) and lower (spinal cord) motor neurons and muscle denervation concisely condenses the clinical picture of amyotrophic lateral sclerosis (ALS). Despite the multiple mechanisms believed to underlie the selective loss of motor neurons, ALS aetiology remains elusive and obscure. Likewise, there is also a cluster of alterations in ALS patients in which muscle wasting, body weight loss, eating dysfunction, and abnormal energy dissipation coexist. Defective energy metabolism characterizes the ALS progression, and such paradox of energy balance stands as a challenge for the understanding of ALS pathogenesis. The hypermetabolism in ALS will be examined from tissue-specific energy imbalance (e.g., skeletal muscle) to major energetic pathways (e.g., AMP-activated protein kinase) and whole-body energy alterations including glucose and lipid metabolism, nutrition, and potential involvement of interorgan communication. From the point of view here expressed, the hypermetabolism in ALS should be evaluated as a magnifying glass through which looking at the ALS pathogenesis is from a different perspective in which defective metabolism can disclose novel mechanistic interpretations and lines of intervention.
进行性和致命性的上运动神经元（大脑）和下运动神经元（脊髓）的丧失以及肌肉失神经支配，简要概括了肌萎缩侧索硬化症（ALS）的临床特征。尽管有多种被认为是导致运动神经元选择性丧失的机制，但 ALS 的病因仍然难以捉摸。同样，在 ALS 患者中也存在一系列改变，其中包括肌肉萎缩、体重减轻、进食功能障碍和能量异常消耗并存。能量代谢缺陷是 ALS 进展的特征，这种能量平衡的悖论是理解 ALS 发病机制的一个挑战。我们将从组织特异性能量失衡（如骨骼肌）到主要能量途径（如 AMP 激活蛋白激酶）以及包括葡萄糖和脂质代谢、营养和潜在的器官间通讯在内的全身能量变化来检查 ALS 中的代谢亢进。从这里表达的观点来看，应该将 ALS 中的代谢亢进评估为一个放大镜，通过它从不同的角度来看待 ALS 的发病机制，在这个角度下，代谢缺陷可以揭示新的机制解释和干预途径。
