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Glucose Metabolic Dysfunction in Neurodegenerative Diseases—New Mechanistic Insights and the Potential of Hypoxia as a Prospective Therapy Targeting Metabolic Reprogramming

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Han, Rongrong, Liang, Jing, Zhou, Bing·2021·International Journal of Molecular Sciences
DOI 10.3390/ijms22115887PMC PMC8198281
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Abstract

Glucose is the main circulating energy substrate for the adult brain. Owing to the high energy demand of nerve cells, glucose is actively oxidized to produce ATP and has a synergistic effect with mitochondria in metabolic pathways. The dysfunction of glucose metabolism inevitably disturbs the normal functioning of neurons, which is widely observed in neurodegenerative disease. Understanding the mechanisms of metabolic adaptation during disease progression has become a major focus of research, and interventions in these processes may relieve the neurons from degenerative stress. In this review, we highlight evidence of mitochondrial dysfunction, decreased glucose uptake, and diminished glucose metabolism in different neurodegeneration models such as Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington’s disease (HD). We also discuss how hypoxia, a metabolic reprogramming strategy linked to glucose metabolism in tumor cells and normal brain cells, and summarize the evidence for hypoxia as a putative therapy for general neurodegenerative disease.

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200 of 205 shown

Cited by

Sorted by citations

Authors
Han, R., Liang, J., & Zhou, B.
Affiliations
Beihang University (CN)
Corresponding author
Zhou, Bing
ORCID
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2021-05-31
Volume
22
Issue
11
Pages
5887
ISSN
1422-0067 (ISSN-L)
DOI
10.3390/ijms22115887
PMC
PMC8198281
OpenAlex
W3164190411
Cited by
125
References
21
Citations by year
2026: 27 · 2025: 33 · 2024: 20 · 2023: 18 · 2022: 23 · 2021: 4
FWCI
1.73
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
China Postdoctoral Science Foundation (2020M670103)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Keywords
glucose metabolism, neurodegenerative diseases, hypoxia, metabolic reprogramming, mitochondrial dysfunction, glucose uptake, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, brain energy metabolism, therapeutic target
MeSH terms
Animals, Hypoxia, Brain, Disease Susceptibility, Energy Metabolism, Glucose, Humans, Neurons, Oxidation-Reduction, Reactive Oxygen Species, Disease Management, Neurodegenerative Diseases, Carbohydrate Metabolism, Molecular Targeted Therapy, Cellular Reprogramming

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