Brain energy rescue: an emerging therapeutic concept for neurodegenerative disorders of ageing.

Autor: Cunnane SC; Department of Medicine, Université de Sherbrooke, Sherbrooke, QC, Canada. stephen.cunnane@usherbrooke.ca.; Research Center on Aging, Sherbrooke, QC, Canada. stephen.cunnane@usherbrooke.ca., Trushina E; Department of Neurology, Mayo Clinic, Rochester, MN, USA., Morland C; Department of Pharmaceutical Biosciences, Institute of Pharmacy, University of Oslo, Oslo, Norway., Prigione A; Department of General Pediatrics, Neonatology, and Pediatric Cardiology, University of Dusseldorf, Dusseldorf, Germany., Casadesus G; Department of Biological Sciences, Kent State University, Kent, OH, USA., Andrews ZB; Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia.; Department of Physiology, Monash University, Clayton, VIC, Australia., Beal MF; Department of Neurology, Weill Cornell Medicine, New York, NY, USA., Bergersen LH; Department of Anatomy, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway., Brinton RD; College of Medicine, University of Arizona, Tucson, AZ, USA., de la Monte S; Brown Medical School, Rhode Island Hospital, Providence, RI, USA., Eckert A; University of Basel, Basel, Switzerland., Harvey J; Ninewells Hospital, University of Dundee, Dundee, UK.; Medical School, University of Dundee, Dundee, UK., Jeggo R; Centre for Therapeutic Innovation in Neuropsychiatry, Institut de Recherche Servier, Croissy sur Seine, France., Jhamandas JH; Department of Medicine, University of Albeta, Edmonton, AB, Canada.; Neuroscience and Mental Health Institute, University of Albeta, Edmonton, AB, Canada., Kann O; Institute of Physiology and Pathophysiology, University of Heidelberg, Heidelberg, Germany., la Cour CM; Centre for Therapeutic Innovation in Neuropsychiatry, Institut de Recherche Servier, Croissy sur Seine, France., Martin WF; Institute of Molecular Evolution, University of Dusseldorf, Dusseldorf, Germany., Mithieux G; Lyon Est University, Lyon, France.; INSERM U1213, Lyon, France., Moreira PI; CNC Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.; Faculty of Medicine, University of Coimbra, Coimbra, Portugal., Murphy MP; MRC Mitochondrial Biology Unit, University of Cambridge, Cambridge, UK., Nave KA; Department of Biosciences, University of Heidelberg, Heidelberg, Germany., Nuriel T; Columbia University Medical Center, New York, NY, USA., Oliet SHR; Neurocentre Magendie, INSERM U1215, Bordeaux, France.; Université de Bordeaux, Bordeaux, France., Saudou F; University of Grenoble Alpes, Grenoble, France.; INSERM U1216, CHU Grenoble Alpes, Grenoble Institute Neurosciences, Grenoble, France., Mattson MP; Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Swerdlow RH; University of Kansas Alzheimer's Disease Center, Fairway, KS, USA., Millan MJ; Centre for Therapeutic Innovation in Neuropsychiatry, Institut de Recherche Servier, Croissy sur Seine, France. mark.millan@servier.com.
Jazyk: angličtina
Zdroj: Nature reviews. Drug discovery [Nat Rev Drug Discov] 2020 Sep; Vol. 19 (9), pp. 609-633. Date of Electronic Publication: 2020 Jul 24.
DOI: 10.1038/s41573-020-0072-x
Abstrakt: 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.
Databáze: MEDLINE