期刊
NATURE REVIEWS DRUG DISCOVERY
卷 19, 期 9, 页码 609-633出版社
NATURE RESEARCH
DOI: 10.1038/s41573-020-0072-x
关键词
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资金
- Advances in Neuroscience for Medical Innovation
- Alzheimer's Association (USA)
- Canadian Institutes of Health Research
- Fonds de Recherche du Quebec -Sante
- Natural Sciences and Engineering Research Council of Canada
- Nestle
- US National Institutes of Health (NIH) [P30 AG035982, R01 AG060733, R01 AG061194]
- NIH National Institute on Aging [RF1AG55549]
- National Institute of Neurological Disorders and Stroke [R01NS107265, RO1AG062135]
- National Health and Medical Research Council of Australia [APP1154974]
- Alzheimer's Association [NIRG-13-282387]
- European Regional Development Fund funds through the operational programme 'Thematic Factors of Competitiveness'
- Portuguese Foundation for Science and Technology [PEst-C/SAU/LA0001/2013-2014, UIDB/04539/2020]
- NIH [1R15AG050292, 1R21AG064479]
- National Institute on Aging [R37AG053589, R01AG057931, P01-AG026572]
- Alberta Prion Research Institute
- Alzheimer's Society of Alberta and Northwest Territories
- University Hospital Foundation (Edmonton, AB, Canada)
- Nasjonalforeningen--Demensforbundet, Norway
- Swiss National Science Foundation [31003A-179294]
- Deutsche Forschungsgemeinschaft [CRC 1134, PR1527/5-1]
- UK Medical Research Council [MC U105663142]
- Wellcome Trust Investigator Award [110159/Z/15/Z]
- European Research Council under the European Union's Horizon 2020 research and innovation programme (ADG) [834317]
- European Research Council [ADG 666053, VW 93046, ADG 671048]
- German Federal Ministry of Education and Research [AZ.031A318, 031L0211]
- Adelson Medical Research Foundation
- Research Council of Norway [262647/F20]
- MRC [MC_UU_00015/3, MC_U105663142] Funding Source: UKRI
- Swiss National Science Foundation (SNF) [31003A_179294] Funding Source: Swiss National Science Foundation (SNF)
- European Research Council (ERC) [834317] Funding Source: European Research Council (ERC)
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. 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.
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