Abstract
Glucose is the main circulating energy substrate for the adult brain. Owing to the high energy demand of nerve cells, glucose is actively oxidized to produce ATP and has a synergistic effect with mitochondria in metabolic pathways. The dysfunction of glucose metabolism inevitably disturbs the normal functioning of neurons, which is widely observed in neurodegenerative disease. Understanding the mechanisms of metabolic adaptation during disease progression has become a major focus of research, and interventions in these processes may relieve the neurons from degenerative stress. In this review, we highlight evidence of mitochondrial dysfunction, decreased glucose uptake, and diminished glucose metabolism in different neurodegeneration models such as Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington’s disease (HD). We also discuss how hypoxia, a metabolic reprogramming strategy linked to glucose metabolism in tumor cells and normal brain cells, and summarize the evidence for hypoxia as a putative therapy for general neurodegenerative disease.
Highlights
It only accounts for 2% of the body’s total weight, the brain has a high demand for energy compared to other tissues
Increasing studies have found that an abnormal glucose metabolism, including mitochondrial dysfunction, is related to the development of neurodegenerative diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington’s disease (HD), which makes it promising to find a solution to these changes, which could improve the quality of life and prolong the survival of patients with neurodegenerative diseases
The NADH produced during glycolysis and NADH and FADH2 produced during the TCA cycle is subsequently re-oxidized in the electron transport chain (ETC), which uses the energy generated by electron transfer through four major protein–metal complexes to transport protons across the inner mitochondrial membrane to the intermembrane space
Summary
It only accounts for 2% of the body’s total weight, the brain has a high demand for energy compared to other tissues. Glucose metabolism promotes the physiological functions of the brain through glycolysis and mitochondrial oxidative phosphorylation, and its product, ATP, is the electrochemical basis for the maintenance of neurons and non-neuronal cells [2]. The NADH produced during glycolysis and NADH and FADH2 produced during the TCA cycle is subsequently re-oxidized in the electron transport chain (ETC), which uses the energy generated by electron transfer through four major protein–metal complexes to transport protons across the inner mitochondrial membrane to the intermembrane space. The PPP metabolizes G6P and generates NADPH, which is used for defense against oxidative stress and biosynthetic reactions It produces ribulose-5-phosphate that can convert to ribose-5-phosphate and is used in the biosynthesis of purine ribonucleotides or intermediates for other pathways. Glycogen turnover is highly regulated to maintain normal functions [16], and its dysregulation with an abnormal accumulation of glycogen structures in the brain causes severe seizures and death in patients with Lafora disease [17]
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