| Literature DB >> 32709961 |
Stephen C Cunnane1,2, Mark J Millan3, Eugenia Trushina4, Cecilie Morland5, Alessandro Prigione6, Gemma Casadesus7, Zane B Andrews8,9, M Flint Beal10, Linda H Bergersen11, Roberta D Brinton12, Suzanne de la Monte13, Anne Eckert14, Jenni Harvey15,16, Ross Jeggo17, Jack H Jhamandas18,19, Oliver Kann20, Clothide Mannoury la Cour17, William F Martin21, Gilles Mithieux22,23, Paula I Moreira24,25, Michael P Murphy26, Klaus-Armin Nave27, Tal Nuriel28, Stéphane H R Oliet29,30, Frédéric Saudou31,32, Mark P Mattson33, Russell H Swerdlow34.
Abstract
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.Entities:
Mesh：
Year: 2020 PMID： 32709961 PMCID： PMC7948516 DOI： 10.1038/s41573-020-0072-x
Source DB: PubMed Journal: Nat Rev Drug Discov ISSN： 1474-1776 Impact factor: 84.694