Pokotylo Marta, Brüggemann Norbert, Prasuhn Jannik
Department of Neurology, University of Medical Center Schleswig-Holstein, Campus Lübeck, Lübeck, Germany.
Center for Brain, Behaviour, and Metabolism, University of Lübeck, Lübeck, Germany.
Aging Dis. 2025 Jun 22;16(5):2721-2738. doi: 10.14336/AD.2025.0619.
Parkinson's disease (PD) is a progressive neurodegenerative condition affecting around 1-2% of the population over the age of 60. The lack of disease-modifying therapies highlights the need for insights into the etiology and pathogenesis of PD. Mitochondrial dysfunction is recognized to be a significant contributor to disease pathogenesis, resulting in bioenergetic deficits and subsequent neurodegeneration. Research indicates that changes in non-oxidative phosphorylation (non-OXPHOS) metabolism in PD may serve as an adaptive response to mitochondrial dysfunction, compensating for energetic failure and alleviating disease progression. This review explores mitochondrial dysfunction-driven alterations in non-OXPHOS metabolic pathways, such as glycolysis and the tricarboxylic acid cycle, emphasizing their role in maintaining energy metabolism and their dual contribution to neuroprotection and disease progression. Advances in neuroimaging techniques are also discussed, particularly their role in visualizing metabolic changes in vivo and their potential utility in identifying non-OXPHOS metabolism as a biomarker of mitochondrial dysfunction. By enhancing our understanding of the complex interplay between metabolic pathways in PD, this review underscores the importance of personalized therapeutic approaches that consider individual metabolic variations. Ultimately, these insights aim to pave the way for improved diagnostic utility and personalized treatment strategies that address the metabolic and mitochondrial dysfunctions underlying PD pathogenesis.
帕金森病（PD）是一种进行性神经退行性疾病，影响着约1%-2%的60岁以上人群。缺乏疾病修饰疗法凸显了深入了解PD病因和发病机制的必要性。线粒体功能障碍被认为是疾病发病机制的一个重要因素，导致生物能量不足及随后的神经退行性变。研究表明，PD中非氧化磷酸化（非OXPHOS）代谢的变化可能是对线粒体功能障碍的一种适应性反应，可补偿能量衰竭并减轻疾病进展。本综述探讨了线粒体功能障碍驱动的非OXPHOS代谢途径（如糖酵解和三羧酸循环）的改变，强调了它们在维持能量代谢中的作用以及它们对神经保护和疾病进展的双重影响。还讨论了神经成像技术的进展，特别是它们在体内可视化代谢变化中的作用以及它们在将非OXPHOS代谢鉴定为线粒体功能障碍生物标志物方面的潜在用途。通过加深我们对PD中代谢途径之间复杂相互作用的理解，本综述强调了考虑个体代谢差异的个性化治疗方法的重要性。最终，这些见解旨在为提高诊断效用和针对PD发病机制基础的代谢和线粒体功能障碍的个性化治疗策略铺平道路。
