Metabolic Dysregulation in Parkinson's Disease: Non-Oxidative Phosphorylation and Its Role in Brain Energy Metabolism.

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.