Volonté Cinzia, Parisi Chiara, Apolloni Savina
Institute of Cell Biology and Neurobiology, CNR, Via del Fosso di Fiorano, 65, 00143 Rome, Italy.
CNS Neurol Disord Drug Targets. 2015;14(5):677-86. doi: 10.2174/1871527314666150225143921.
Results from amyotrophic lateral sclerosis (ALS) patients and pre-clinical studies strongly suggest that systemic and CNS-intrinsic immune activation plays a central role in ALS pathogenesis. Microglial cells are emerging in this context as master regulators with a bi-functional role in the progression of the pathological response. They foster a pro-inflammatory setting through the production of cytotoxic cytokines and chemokines (M1 phenotype), after an aborted effort to sustain an anti-inflammatory environment for motor neurons through the release of beneficial cytokines and growth factors (M2 phenotype). In this review, we gather information meant to propose that histamine and ATP, which are released from mast cells, microglia and damaged neurons at sites of injury where they function as transmitters, have to be considered as new players in the ALS neuroinflammatory arena. After all, abnormal histamine and ATP signalling in the brain are already documented in neurodegenerative/neuroinflammatory conditions such as multiple sclerosis, Alzheimer and Parkinson's disease and, at present, histamine- as well as ATP-related compounds are in clinical trial for these same pathologies. Concerning ALS, while emerging data are now available about purinergic mechanisms, the involvement of histamine is basically unexplored. The circumstantial evidence that we present here thus constitutes a solid background for formulating novel hypotheses, stimulating a scientific debate and, most of all, inspiring future research. We deem that a new potential role of histamine in the setting of ALS neuroinflammation might find a fertile ground where to thrive. ALS is still a disease without a cure: why not to play with a new kid on the block?
肌萎缩侧索硬化症（ALS）患者的研究结果以及临床前研究强烈表明，全身和中枢神经系统内在的免疫激活在ALS发病机制中起核心作用。在这种情况下，小胶质细胞作为主要调节因子出现，在病理反应进展中具有双重功能。在试图通过释放有益细胞因子和生长因子为运动神经元维持抗炎环境的努力失败后，它们通过产生细胞毒性细胞因子和趋化因子（M1表型）促进促炎环境。在这篇综述中，我们收集了相关信息，旨在提出组胺和三磷酸腺苷（ATP）应被视为ALS神经炎症领域的新参与者，它们在损伤部位从肥大细胞、小胶质细胞和受损神经元中释放出来，发挥递质的作用。毕竟，大脑中组胺和ATP信号异常在神经退行性/神经炎症性疾病如多发性硬化症、阿尔茨海默病和帕金森病中已有记载，目前，组胺以及与ATP相关的化合物正在针对这些相同病症进行临床试验。关于ALS，虽然现在已有关于嘌呤能机制的新数据，但组胺的参与基本上尚未得到探索。我们在此提供的间接证据因此构成了一个坚实的背景，用于提出新的假设、激发科学辩论，最重要的是，启发未来的研究。我们认为组胺在ALS神经炎症中的新潜在作用可能会找到一个蓬勃发展的沃土。ALS仍然是一种无法治愈的疾病：为什么不试试这个新角色呢？
