Vermeiren Yannick, Janssens Jana, Van Dam Debby, De Deyn Peter P
Laboratory of Neurochemistry and Behavior, Department of Biomedical Sciences, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
Department of Neurology and Alzheimer Research Center, University of Groningen and University Medical Center Groningen, Groningen, Netherlands.
Front Neurosci. 2018 Mar 20;12:185. doi: 10.3389/fnins.2018.00185. eCollection 2018.
Amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD) share similar pathophysiological mechanisms. From a neurochemical point of view, the serotonin (5-hydroxytryptamine; 5-HT) dysfunction in both movement disorders-related to probable lesioning of the raphe nuclei-is profound, and, therefore, may be partially responsible for motor as well as non-motor disturbances. More specifically, in ALS, it has been hypothesized that serotonergic denervation leads to loss of its inhibitory control on glutamate release, resulting into glutamate-induced neurotoxicity in lower and/or upper motor neurons, combined with a detrimental decrease of its facilitatory effects on glutamatergic motor neuron excitation. Both events then may eventually give rise to the well-known clinical motor phenotype. Similarly, disruption of the organized serotonergic control on complex mesencephalic dopaminergic connections between basal ganglia (BG) nuclei and across the BG-cortico-thalamic circuits, has shown to be closely involved in the onset of parkinsonian symptoms. Levodopa (L-DOPA) therapy in PD largely seems to confirm the influential role of 5-HT, since serotonergic rather than dopaminergic projections release L-DOPA-derived dopamine, particularly in extrastriatal regions, emphasizing the strongly interwoven interactions between both monoamine systems. Apart from its orchestrating function, the 5-HT system also exerts neuroprotective and anti-inflammatory effects. In line with this observation, emerging therapies have recently focused on boosting the serotonergic system in ALS and PD, which may provide novel rationale for treating these devastating conditions both on the disease-modifying, as well as symptomatic level.
肌萎缩侧索硬化症（ALS）和帕金森病（PD）具有相似的病理生理机制。从神经化学角度来看，这两种与中缝核可能受损相关的运动障碍中，血清素（5-羟色胺；5-HT）功能障碍都很严重，因此，可能部分导致运动及非运动障碍。更具体地说，在ALS中，有人提出血清素能去神经支配导致对谷氨酸释放的抑制控制丧失，从而导致谷氨酸诱导的下运动神经元和/或上运动神经元神经毒性，同时其对谷氨酸能运动神经元兴奋的促进作用也有害性降低。这两个事件最终可能导致众所周知的临床运动表型。同样，有组织的血清素能对基底神经节（BG）核之间以及BG-皮质-丘脑回路之间复杂的中脑多巴胺能连接的控制被破坏，已被证明与帕金森症状的发作密切相关。PD中的左旋多巴（L-DOPA）治疗在很大程度上似乎证实了5-HT的影响作用，因为血清素能而非多巴胺能投射释放L-DOPA衍生的多巴胺，特别是在纹状体以外的区域，这强调了这两种单胺系统之间强烈的相互交织作用。除了其协调功能外，5-HT系统还具有神经保护和抗炎作用。与此观察结果一致，最近新兴的治疗方法集中在增强ALS和PD中的血清素能系统，这可能为在疾病修饰以及症状水平上治疗这些毁灭性疾病提供新的理论依据。
