Elevation of AKR7A2 (succinic semialdehyde reductase) in neurodegenerativedisease

Citation
Mj. Picklo et al., Elevation of AKR7A2 (succinic semialdehyde reductase) in neurodegenerativedisease, BRAIN RES, 916(1-2), 2001, pp. 229-238
Citations number
57
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences & Behavoir
Journal title
BRAIN RESEARCH
ISSN journal
0006-8993 → ACNP
Volume
916
Issue
1-2
Year of publication
2001
Pages
229 - 238
Database
ISI
SICI code
0006-8993(20011019)916:1-2<229:EOA(SR>2.0.ZU;2-8
Abstract
Elevated levels of oxidative stress or decreased antioxidant defense mechan isms may underlie the regionally increased oxidative damage to brain observ ed in many neurodegenerative disorders. Phase I detoxification pathways for reactive aldehydes generated from lipid peroxidation include aldehyde dehy drogenases, alcohol dehydrogenases and aldo-keto reductases (AKR). In the p resent study, we examined the cellular expression of AKR family member, suc cinic semialdehyde reductase (AKR7A2) that reduces toxic aldehydes as well as catalyzing the biosynthesis of the neuromodulator gamma -hydroxybutyrate (GHB). Our results show that in the cerebral cortex and hippocampus, AKR7A 2 is primarily localized to glial cells, astrocytes and microglia. In the m idbrain, AKR7A2 was found in glia and neuromelanin-containing neurons of th e substantia nigra, and the periaqueductal gray. In sections of cerebral co rtex and hippocampus from patients with AD and DLB, AKR7A2 immunoreactivity was elevated in reactive astrocytes and microglial cells. Furthermore, tot al AKR7A2 protein levels were elevated in the cerebral cortex of patients w ith AD versus control individuals. Our data suggest that reactive gliosis, as a response to injury, may affect GHB neuromodulatory pathways in neurode generative disease and elevate aldehyde detoxification pathways. (C) 2001 E lsevier Science B.V. All rights reserved.