Phillipson Oliver T
School of Medical Sciences, University of Bristol, University Walk, Bristol, UK.
Neurobiol Aging. 2014 Apr;35(4):847-57. doi: 10.1016/j.neurobiolaging.2013.10.073. Epub 2013 Oct 10.
The aging risk factor for Parkinson's disease is described in terms of specific disease markers including mitochondrial and gene dysfunctions relevant to energy metabolism. This review details evidence for the ability of nutritional agents to manage these aging risk factors. The combination of alpha lipoic acid, acetyl-l-carnitine, coenzyme Q10, and melatonin supports energy metabolism via carbohydrate and fatty acid utilization, assists electron transport and adenosine triphosphate synthesis, counters oxidative and nitrosative stress, and raises defenses against protein misfolding, inflammatory stimuli, iron, and other endogenous or xenobiotic toxins. These effects are supported by gene expression via the antioxidant response element (ARE; Keap/Nrf2 pathway), and by peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC-1 alpha), a transcription coactivator, which regulates gene expression for energy metabolism and mitochondrial biogenesis, and maintains the structural integrity of mitochondria. The effectiveness and synergies of the combination against disease risks are discussed in relation to gene action, dopamine cell loss, and the accumulation and spread of pathology via misfolded alpha-synuclein. In addition there are potential synergies to support a neurorestorative role via glial derived neurotrophic factor expression.
帕金森病的衰老风险因素是根据特定的疾病标志物来描述的，这些标志物包括与能量代谢相关的线粒体和基因功能障碍。本综述详细阐述了营养剂管理这些衰老风险因素能力的证据。α-硫辛酸、乙酰左旋肉碱、辅酶Q10和褪黑素的组合通过碳水化合物和脂肪酸利用来支持能量代谢，协助电子传递和三磷酸腺苷合成，对抗氧化应激和亚硝化应激，并增强对蛋白质错误折叠、炎症刺激、铁及其他内源性或外源性毒素的防御。这些作用通过抗氧化反应元件（ARE；Keap/Nrf2途径）以及过氧化物酶体增殖物激活受体γ共激活因子1α（PGC-1α，一种转录共激活因子）的基因表达得到支持，PGC-1α调节能量代谢和线粒体生物发生的基因表达，并维持线粒体的结构完整性。结合物针对疾病风险的有效性和协同作用，是围绕基因作用、多巴胺能细胞丢失以及通过错误折叠的α-突触核蛋白导致的病理积累和扩散来讨论的。此外，通过胶质细胞源性神经营养因子表达，可能存在支持神经修复作用的协同效应。
