TY - JOUR
T1 - Brain energy rescue
T2 - an emerging therapeutic concept for neurodegenerative disorders of ageing
AU - Cunnane, Stephen C.
AU - Trushina, Eugenia
AU - Morland, Cecilie
AU - Prigione, Alessandro
AU - Casadesus, Gemma
AU - Andrews, Zane B.
AU - Beal, M. Flint
AU - Bergersen, Linda H.
AU - Brinton, Roberta D.
AU - de la Monte, Suzanne
AU - Eckert, Anne
AU - Harvey, Jenni
AU - Jeggo, Ross
AU - Jhamandas, Jack H.
AU - Kann, Oliver
AU - la Cour, Clothide Mannoury
AU - Martin, William F.
AU - Mithieux, Gilles
AU - Moreira, Paula I.
AU - Murphy, Michael P.
AU - Nave, Klaus Armin
AU - Nuriel, Tal
AU - Oliet, Stéphane H.R.
AU - Saudou, Frédéric
AU - Mattson, Mark P.
AU - Swerdlow, Russell H.
AU - Millan, Mark J.
N1 - Publisher Copyright:
© 2020, Springer Nature Limited.
PY - 2020/9/1
Y1 - 2020/9/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85088568260&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85088568260&partnerID=8YFLogxK
U2 - 10.1038/s41573-020-0072-x
DO - 10.1038/s41573-020-0072-x
M3 - Review article
C2 - 32709961
AN - SCOPUS:85088568260
SN - 1474-1776
VL - 19
SP - 609
EP - 633
JO - Nature Reviews Drug Discovery
JF - Nature Reviews Drug Discovery
IS - 9
ER -