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Sugar for the brain: the role of glucose in physiological and pathological brain function.The mammalian brain depends upon glucose as its main source of energy, and tight regulation of glucose metabolism is critical for brain physiology. Consistent with its critical role for physiological brain function, disruption of normal glucose metabolism as well as its interdependence with cell death pathways forms the pathophysiological basis for many brain disorders. Here, we review recent advances in understanding how glucose metabolism sustains basic brain physiology. We aim at synthesizing these findings to form a comprehensive picture of the cooperation required between different systems and cell types, and the specific breakdowns in this cooperation which lead to disease.The mammalian brain depends on glucose as its main source of energy. In the adult brain, neurons have the highest energy demand [1], requiring continuous delivery of glucose from blood. In humans, the brain accounts for ~2% of the body weight, but it consumes ~20% of glucose-derived energy making it the main consumer of glucose (~5.6 mg glucose per 100 g human brain tissue per minute [2]). Glucose metabolism provides the fuel for physiological brain function through the generation of ATP, the foundation for neuronal and non-neuronal cellular maintenance, as well as the generation of neurotransmitters. Therefore, tight regulation of glucose metabolism is critical for brain physiology and disturbed glucose metabolism in the brain underlies several diseases affecting both the brain itself as well as the entire organism.
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