Amyloid-β triggers the release of neuronal Hexokinase 1 from mitochondria

Leonardo M. Saraiva, Gisele S. Seixas da Silva, Antonio Galina, Wagner S. da-Silva, William L. Klein, Sérgio T. Ferreira, Fernanda G. de Felice

Research output: Contribution to journalArticle

58 Scopus citations

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.

Original languageEnglish (US)
Article numbere15230
JournalPloS one
Volume5
Issue number12
DOIs
StatePublished - 2010

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Saraiva, L. M., Seixas da Silva, G. S., Galina, A., da-Silva, W. S., Klein, W. L., Ferreira, S. T., & de Felice, F. G. (2010). Amyloid-β triggers the release of neuronal Hexokinase 1 from mitochondria. PloS one, 5(12), [e15230]. https://doi.org/10.1371/journal.pone.0015230