Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur Street, 02-093 Warsaw, Poland.
Division of Neuropathology, Department of Pathology and Molecular Pathology, Neuromed Campus, Kepler University Hospital, Johannes Kepler University, A-4020 Linz, Austria.
Int J Mol Sci. 2021 Mar 16;22(6):3016. doi: 10.3390/ijms22063016.
Parkinson's disease (PD) is a neurodegenerative disorder that manifests with rest tremor, muscle rigidity and movement disturbances. At the microscopic level it is characterized by formation of specific intraneuronal inclusions, called Lewy bodies (LBs), and by a progressive loss of dopaminergic neurons in the striatum and substantia nigra. All living cells, among them neurons, rely on Ca as a universal carrier of extracellular and intracellular signals that can initiate and control various cellular processes. Disturbances in Ca homeostasis and dysfunction of Ca signaling pathways may have serious consequences on cells and even result in cell death. Dopaminergic neurons are particularly sensitive to any changes in intracellular Ca level. The best known and studied Ca sensor in eukaryotic cells is calmodulin. Calmodulin binds Ca with high affinity and regulates the activity of a plethora of proteins. In the brain, calmodulin and its binding proteins play a crucial role in regulation of the activity of synaptic proteins and in the maintenance of neuronal plasticity. Thus, any changes in activity of these proteins might be linked to the development and progression of neurodegenerative disorders including PD. This review aims to summarize published results regarding the role of calmodulin and its binding proteins in pathology and pathogenesis of PD.
帕金森病（PD）是一种神经退行性疾病，表现为静止性震颤、肌肉僵硬和运动障碍。在微观水平上，它的特征是形成特定的神经元内包涵体，称为路易体（LB），以及纹状体和黑质中多巴胺能神经元的进行性丧失。所有的活细胞，包括神经元，都依赖 Ca 作为细胞外和细胞内信号的通用载体，这些信号可以启动和控制各种细胞过程。Ca 稳态的紊乱和 Ca 信号通路的功能障碍可能对细胞产生严重后果，甚至导致细胞死亡。多巴胺能神经元对细胞内 Ca 水平的任何变化都特别敏感。真核细胞中最著名和研究最多的 Ca 传感器是钙调蛋白。钙调蛋白与 Ca 具有高亲和力结合，并调节大量蛋白质的活性。在大脑中，钙调蛋白及其结合蛋白在调节突触蛋白的活性和维持神经元可塑性方面起着至关重要的作用。因此，这些蛋白质活性的任何变化都可能与包括 PD 在内的神经退行性疾病的发展和进展有关。这篇综述旨在总结关于钙调蛋白及其结合蛋白在 PD 病理和发病机制中的作用的已发表结果。
