PDF(Pubmed)
Abstract：
Parkinson\'s disease (PD) is a progressive neurodegenerative disorder that lacks effective treatment strategies to halt or delay its progression. The homeostasis of Ca2+ ions is crucial for ensuring optimal cellular functions and survival, especially for neuronal cells. In the context of PD, the systems regulating cellular Ca2+ are compromised, leading to Ca2+-dependent synaptic dysfunction, impaired neuronal plasticity, and ultimately, neuronal loss. Recent research efforts directed toward understanding the pathology of PD have yielded significant insights, particularly highlighting the close relationship between Ca2+ dysregulation, neuroinflammation, and neurodegeneration. However, the precise mechanisms driving the selective loss of dopaminergic neurons in PD remain elusive. The disruption of Ca2+ homeostasis is a key factor, engaging various neurodegenerative and neuroinflammatory pathways and affecting intracellular organelles that store Ca2+. Specifically, impaired functioning of mitochondria, lysosomes, and the endoplasmic reticulum (ER) in Ca2+ metabolism is believed to contribute to the disease\'s pathophysiology. The Na+-Ca2+ exchanger (NCX) is considered an important key regulator of Ca2+ homeostasis in various cell types, including neurons, astrocytes, and microglia. Alterations in NCX activity are associated with neurodegenerative processes in different models of PD. In this review, we will explore the role of Ca2+ dysregulation and neuroinflammation as primary drivers of PD-related neurodegeneration, with an emphasis on the pivotal role of NCX in the pathology of PD. Consequently, NCXs and their interplay with intracellular organelles may emerge as potentially pivotal players in the mechanisms underlying PD neurodegeneration, providing a promising avenue for therapeutic intervention aimed at halting neurodegeneration.
摘要：
帕金森病（PD）是一种进行性神经退行性疾病，缺乏有效的治疗策略来阻止或延缓其进展。Ca2+离子的稳态对于确保最佳的细胞功能和存活至关重要。尤其是神经元细胞。在PD的背景下，调节细胞Ca2+的系统受损，导致Ca2+依赖性突触功能障碍，神经元可塑性受损，最终,神经元丢失。最近针对了解PD病理学的研究努力已经产生了重要的见解，特别强调Ca2+失调之间的密切关系，神经炎症，和神经变性。然而,导致PD中多巴胺能神经元选择性丢失的确切机制仍然难以捉摸。Ca2+稳态的破坏是一个关键因素，参与各种神经退行性和神经炎症途径，并影响储存Ca2+的细胞内细胞器。具体来说,线粒体功能受损，溶酶体,和内质网（ER）在Ca2+代谢被认为是促进疾病的病理生理。Na+-Ca2+交换剂(NCX)被认为是各种细胞类型中Ca2+稳态的重要关键调节剂。包括神经元，星形胶质细胞,和小胶质细胞.NCX活性的改变与不同PD模型中的神经变性过程相关。在这次审查中,我们将探讨Ca2+失调和神经炎症作为PD相关神经变性的主要驱动因素的作用，强调NCX在PD病理学中的关键作用。因此,NCXs及其与细胞内细胞器的相互作用可能成为PD神经变性机制的潜在关键参与者，为旨在停止神经变性的治疗干预提供了有希望的途径。
