Department of Anatomy, Faculty of Medicine, Jordan University of Science and Technology, 22110 Irbid, Jordan.
J Integr Neurosci. 2022 Jan 28;21(1):30. doi: 10.31083/j.jin2101030.
Apoptosis, autophagy and necrosis are the three main types of programmed cell death. One or more of these types of programmed cell death may take place in neurons leading to their death in various neurodegenerative disorders in humans. Purkinje neurons (PNs) are among the most highly vulnerable population of neurons to cell death in response to intrinsic hereditary diseases or extrinsic toxic, hypoxic, ischemic, and traumatic injury. In this review, we will describe the three main types of programmed cell death, including the molecular mechanisms and the sequence of events in each of them, and thus illustrating the intracellular proteins that mediate and regulate each of these types. Then, we will discuss the role of Ca2+ in PN function and increased vulnerability to cell death. Additionally, PN death will be described in animal models, namely lurcher mutant mouse and shaker mutant rat, in order to illustrate the potential therapeutic implications of programmed cell death in PNs by reviewing the previous studies that were carried out to interfere with the programmed cell death in an attempt to rescue PNs from death.
细胞凋亡、自噬和坏死是三种主要的程序性细胞死亡类型。在人类的各种神经退行性疾病中，神经元可能会发生一种或多种类型的程序性细胞死亡，导致其死亡。浦肯野神经元 (PNs) 是对内在遗传性疾病或外在毒性、缺氧、缺血和创伤性损伤最易发生细胞死亡的神经元之一。在这篇综述中，我们将描述三种主要的程序性细胞死亡类型，包括它们各自的分子机制和事件顺序，从而阐明介导和调节这些类型的细胞内蛋白。然后，我们将讨论 Ca2+ 在 PN 功能和对细胞死亡易感性增加中的作用。此外，将在动物模型中描述 PN 死亡，即 lurcher 突变小鼠和 shaker 突变大鼠，以通过回顾之前进行的研究来阐明 PN 中程序性细胞死亡的潜在治疗意义，这些研究试图通过干扰程序性细胞死亡来挽救 PN 免于死亡。
