Metabolic Dysfunction in Parkinson’s Disease: Bioenergetics, Redox Homeostasis and Central Carbon Metabolism

• Published in: Brain research bulletin 2017-07, Vol.133, p.12-30
• Main Authors: Anandhan, Annadurai, Jacome, Maria S., Lei, Shulei, Hernandez-Franco, Pablo, Pappa, Aglaia, Panayiotidis, Mihalis I., Powers, Robert, Franco, Rodrigo
• Format: Article
• Language: English
• Subjects: Bioenergetics; Brain - metabolism; Brain Diseases, Metabolic; Carbon - metabolism; Dopaminergic Neurons - metabolism; Energy Metabolism; Glucose; Glycolysis; Homeostasis; Humans; Mitochondria; Mitochondria - metabolism; Neurodegeneration; Oxidation-Reduction; Oxidative stress; Oxidative Stress - physiology; Parkinson Disease - metabolism; Substantia Nigra - metabolism; TCA cycle
• ISSN: 0361-9230; 1873-2747
• DOI: 10.1016/j.brainresbull.2017.03.009

•Mitochondrial dysfunction in PD triggers oxidative stress and energy failure.•We provide an integrated view of bioenergetics, redox and central carbon metabolism in PD.•Clinical trials demonstrate that PD cannot be explained simply by oxidative stress and energy failure.•These findings strengthen the idea that PD is a complex metabolic disorder. The loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the accumulation of protein inclusions (Lewy bodies) are the pathological hallmarks of Parkinson’s disease (PD). PD is triggered by genetic alterations, environmental/occupational exposures and aging. However, the exact molecular mechanisms linking these PD risk factors to neuronal dysfunction are still unclear. Alterations in redox homeostasis and bioenergetics (energy failure) are thought to be central components of neurodegeneration that contribute to the impairment of important homeostatic processes in dopaminergic cells such as protein quality control mechanisms, neurotransmitter release/metabolism, axonal transport of vesicles and cell survival. Importantly, both bioenergetics and redox homeostasis are coupled to neuro-glial central carbon metabolism. We and others have recently established a link between the alterations in central carbon metabolism induced by PD risk factors, redox homeostasis and bioenergetics and their contribution to the survival/death of dopaminergic cells. In this review, we focus on the link between metabolic dysfunction, energy failure and redox imbalance in PD, making an emphasis in the contribution of central carbon (glucose) metabolism. The evidence summarized here strongly supports the consideration of PD as a disorder of cell metabolism.