Valente André X C N, Adilbayeva Altynai, Tokay Tursonjan, Rizvanov Albert A
Center for Neuroscience and Cell Biology, University of Coimbra, Cantanhede, Portugal.
Biocant - Biotechnology Innovation Center, Cantanhede, Portugal.
Cent Asian J Glob Health. 2016 Jun 1;5(1):231. doi: 10.5195/cajgh.2016.231. eCollection 2016.
Parkinson's disease (PD) is one of the most common neurodegenerative disorders, yet the etiology of the majority of its cases remains unknown. In this manuscript, relevant published evidence is interpreted and integrated into a comprehensive hypothesis on the nature, origin, and inter-cellular mode of propagation of sporadic PD. We propose to characterize sporadic PD as a pathological deviation in the global gene expression program of a cell: the PD expression-state, or PD-state for short. A universal cell-generic state, the PD-state deviation would be particularly damaging in a neuronal context, ultimately leading to neuron death and the ensuing observed clinical signs. We review why ageing associated accumulated damage caused by oxidative stress in mitochondria could be the trigger for a primordial cell to shift to the PD-state. We propose that hematopoietic cells could be the first to acquire the PD-state, at hematopoiesis, from the disruption in reactive oxygen species homeostasis that arises with age in the hematopoietic stem-cell niche. We argue that cellular ageing is nevertheless unlikely to explain the shift to the PD-state of all the subsequently affected cells in a patient, thus indicating the existence of a distinct mechanism of cellular propagation of the PD-state. We highlight recently published findings on the inter-cellular exchange of mitochondrial DNA and the ability of mitochondrial DNA to modulate the cellular global gene expression state and propose this could form the basis for the inter-cellular transmission of the PD-state.
帕金森病（PD）是最常见的神经退行性疾病之一，但其大多数病例的病因仍不明。在本论文中，相关已发表证据被解读并整合为一个关于散发性帕金森病的本质、起源及细胞间传播模式的综合假说。我们提议将散发性帕金森病表征为细胞整体基因表达程序中的一种病理偏差：帕金森病表达状态，或简称为PD状态。作为一种普遍的细胞通用状态，PD状态偏差在神经元环境中会造成特别严重的损害，最终导致神经元死亡及随之出现的临床症状。我们回顾了为何线粒体中由氧化应激导致的与衰老相关的累积损伤可能是原始细胞转变为PD状态的触发因素。我们提出造血细胞可能是首个在造血过程中因造血干细胞微环境中随年龄增长而出现的活性氧稳态破坏而获得PD状态的细胞。我们认为细胞衰老不太可能解释患者体内所有后续受影响细胞向PD状态的转变，因此表明存在一种独特的PD状态细胞传播机制。我们强调了最近发表的关于线粒体DNA细胞间交换以及线粒体DNA调节细胞整体基因表达状态能力的研究结果，并提出这可能构成PD状态细胞间传播的基础。
