Anderson George, Maes Michael
CRC, Rm 30, 57 Laurel St., Glasgow, G11 7QT, Scotland, UK,
Mol Neurobiol. 2014 Apr;49(2):771-83. doi: 10.1007/s12035-013-8554-z. Epub 2013 Oct 2.
The biological underpinnings to the etiology and course of neurodegeneration in Parkinson's disease are an area of extensive research that has yet to produce an early biological marker or disease-slowing or preventative treatment. Recent conceptualizations of Parkinson's disease have integrated immuno-inflammation and oxidative and nitrosative stress occurring in depression, somatization and peripheral inflammation into the course of Parkinson's disease. We review the data showing the importance of immuno-inflammatory processes and oxidative and nitrosative stress in such classically conceived 'comorbidities', suggesting that lifetime, prodromal and concurrent depression and somatization may be intricately involved in the etiology and course of Parkinson's disease, rather than psychiatric comorbidities. This produces a longer term developmental perspective of Parkinson's disease, which incorporates tryptophan catabolites (TRYCATs), lipid peroxidation, sirtuins, cyclic adenosine monophosphate, aryl hydrocarbon receptor, and circadian genes. This integrates wider bodies of data pertaining to neuronal loss in Parkinson's disease, emphasizing how these interact with susceptibility genes to drive changes in mitochondria, blood-brain barrier permeability and intercellular signalling. We review this data here in the context of neurodegeneration in Parkinson's disease and to the future directions indicated for slowing disease progression.
帕金森病神经退行性变的病因及病程的生物学基础是一个广泛研究的领域，但尚未产生早期生物学标志物或减缓疾病进展或预防疾病的治疗方法。帕金森病的最新概念已将抑郁症、躯体化障碍和外周炎症中发生的免疫炎症以及氧化应激和亚硝化应激纳入帕金森病的病程。我们回顾了相关数据，这些数据表明免疫炎症过程以及氧化应激和亚硝化应激在这些传统概念中的“共病”中的重要性，这表明一生中、前驱期和并发期的抑郁和躯体化障碍可能与帕金森病的病因及病程密切相关，而非精神科共病。这为帕金森病提供了一个更长期的发展视角，其中包括色氨酸分解代谢产物（TRYCATs）、脂质过氧化、沉默调节蛋白、环磷酸腺苷、芳烃受体和昼夜节律基因。这整合了与帕金森病神经元丢失相关的更广泛的数据，强调了这些因素如何与易感基因相互作用，从而驱动线粒体、血脑屏障通透性和细胞间信号传导的变化。我们在此结合帕金森病神经退行性变的背景对这些数据进行回顾，并探讨减缓疾病进展的未来方向。
