Elevation of AKR7A2 (succinic semialdehyde reductase) in neurodegenerative disease

Matthew J. Picklo, Sandra J. Olson, John Hayes (Lead / Corresponding author), William R. Markesbery, Thomas J. Montine

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    55 Citations (Scopus)


    Elevated levels of oxidative stress or decreased antioxidant defense mechanisms may underlie the regionally increased oxidative damage to brain observed in many neurodegenerative disorders. Phase I detoxification pathways for reactive aldehydes generated from lipid peroxidation include aldehyde dehydrogenases, alcohol dehydrogenases and aldo-keto reductases (AKR). In the present study, we examined the cellular expression of AKR family member, succinic semialdehyde reductase (AKR7A2) that reduces toxic aldehydes as well as catalyzing the biosynthesis of the neuromodulator γ-hydroxybutyrate (GHB). Our results show that in the cerebral cortex and hippocampus, AKR7A2 is primarily localized to glial cells, astrocytes and microglia. In the midbrain, AKR7A2 was found in glia and neuromelanin-containing neurons of the substantia nigra, and the periaqueductal gray. In sections of cerebral cortex and hippocampus from patients with AD and DLB, AKR7A2 immunoreactivity was elevated in reactive astrocytes and microglial cells. Furthermore, total AKR7A2 protein levels were elevated in the cerebral cortex of patients with AD versus control individuals. Our data suggest that reactive gliosis, as a response to injury, may affect GHB neuromodulatory pathways in neurodegenerative disease and elevate aldehyde detoxification pathways.
    Original languageEnglish
    Pages (from-to)229-238
    Number of pages10
    JournalBrain Research
    Issue number1-2
    Early online date17 Aug 2001
    Publication statusPublished - Oct 2001


    • Gamma-hydroxybutyrate
    • Gliosis
    • Aflatoxin aldehyde reductase
    • Lipid peroxidation


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