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Cited by 94Alzheimer's disease research and treatmentsMitochondrial Function and PathologyDementia and Cognitive Impairment Research

Amyloid-β Triggers the Release of Neuronal Hexokinase 1 from Mitochondria

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Saraiva, Leonardo M., Seixas da Silva, Gisele S., Galina, Antonio, da-Silva, Wagner S., Klein, William L., Ferreira, Sérgio T., De Felice, Fernanda G.·2010·PLoS ONE
DOI 10.1371/journal.pone.0015230PMC PMC3002973
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Abstract

Brain accumulation of the amyloid-β peptide (Aβ) and oxidative stress underlie neuronal dysfunction and memory loss in Alzheimer's disease (AD). Hexokinase (HK), a key glycolytic enzyme, plays important pro-survival roles, reducing mitochondrial reactive oxygen species (ROS) generation and preventing apoptosis in neurons and other cell types. Brain isozyme HKI is mainly associated with mitochondria and HK release from mitochondria causes a significant decrease in enzyme activity and triggers oxidative damage. We here investigated the relationship between Aβ-induced oxidative stress and HK activity. We found that Aβ triggered HKI detachment from mitochondria decreasing HKI activity in cortical neurons. Aβ oligomers further impair energy metabolism by decreasing neuronal ATP levels. Aβ-induced HKI cellular redistribution was accompanied by excessive ROS generation and neuronal death. 2-deoxyglucose blocked Aβ-induced oxidative stress and neuronal death. Results suggest that Aβ-induced cellular redistribution and inactivation of neuronal HKI play important roles in oxidative stress and neurodegeneration in AD.

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Cited by

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Authors
Saraiva, L. M., Seixas da Silva, G. S., Galina, A., da-Silva, W. S., Klein, W. L., Ferreira, S. T., & De Felice, F. G.
Affiliations
  • Universidade Federal do Rio de Janeiro (BR)
  • Northwestern University (US)
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2010-12-16
Volume
5
Issue
12
Pages
e15230
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0015230
PMC
PMC3002973
OpenAlex
W2065714966
Cited by
94
References
5
Citations by year
2026: 2 · 2025: 2 · 2024: 8 · 2023: 7 · 2022: 4 · 2021: 3 · 2020: 11 · 2019: 8 · 2018: 4 · 2017: 8 · 2016: 5 · 2015: 7 · 2014: 9 · 2013: 5 · 2012: 5
FWCI
3.25
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Alzheimer's Association
  • American Health Assistance Foundation
  • John Simon Guggenheim Memorial Foundation
  • National Institutes of Health
  • National Institute on Aging (R01AG022547, R01AG018877)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
amyloid-beta, hexokinase 1, oxidative stress, Alzheimer's disease, neurodegeneration, neuronal energy metabolism, ATP depletion, reactive oxygen species, amyloid-beta oligomers, cortical neurons, 2-deoxyglucose, glycolysis
MeSH terms
Animals, Cell Survival, Cytosol, Deoxyglucose, Hexokinase, Humans, Isoenzymes, Mitochondria, Neurons, Tetrazolium Salts, Thiazoles, Amyloid beta-Peptides, Reactive Oxygen Species, Oxidative Stress, Rats

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