Brain energy rescue: an emerging therapeutic concept for neurodegenerative disorders of ageing
By S. Cunnane, E. Trushina, Cecilie Morland, A. Prigione, G. Casadesus, Z. Andrews, M. Beal, L. Bergersen, R. Brinton, S. Monte and 19 more. Nature reviews. Drug discovery, 2020
833 citations recorded by the source corpus.
The brain requires a continuous supply of energy in the form of ATP, most of which is produced from glucose by oxidative phosphorylation in mitochondria, complemented by aerobic glycolysis in the cytoplasm. When glucose levels are limited, ketone bodies generated in the liver and lactate derived from exercising skeletal muscle can also become important energy substrates for the brain. In neurodegenerative disorders of ageing, brain glucose metabolism deteriorates in a progressive, region-specific and disease-specific manner — a problem that is best characterized in Alzheimer disease, where it begins presymptomatically. This Review discusses the status and prospects of therapeutic strategies for countering neurodegenerative disorders of ageing by improving, preserving or rescuing brain energetics. The approaches described include restoring oxidative phosphorylation and glycolysis, increasing insulin sensitivity, correcting mitochondrial dysfunction, ketone-based interventions, acting via hormones that modulate cerebral energetics, RNA therapeutics and complementary multimodal lifestyle changes. Accumulating evidence indicates that impaired glucose metabolism in the brain is involved in the cause and progression of neurodegenerative disorders of ageing such as Alzheimer disease. This Review discusses the status and prospects of therapeutic strategies for countering neurodegenerative disorders of ageing by rescuing, protecting or normalizing brain energetics.
Subfields: Biochemistry, Molecular Biology, Physiology
View Paper: https://www.semanticscholar.org/paper/77d1884fce214050bc2d575f3a736ed94dfabb60
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Citations in the corpus
- Mitochondrial dysfunction: mechanisms and advances in therapy (2024, background): “18,226,391,392 Recently, mitochondrial-targeting therapy has revealed its potential in postponing the pathological course of PD.”
- Hallmarks of neurodegenerative diseases. (2023, positive): “As neurons are highly active and energetically demanding cells of the human body, 98,184 defects in energy metabolism have been shown to participate in many different NDDs 10,11,22,98–100, 104, 185– 191 ( Figures1and3 ).”