RGD Reference Report - Elevation of AKR7A2 (succinic semialdehyde reductase) in neurodegenerative disease. - Rat Genome Database

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Elevation of AKR7A2 (succinic semialdehyde reductase) in neurodegenerative disease.

Authors: Picklo, M J  Olson, S J  Hayes, J D  Markesbery, W R  Montine, T J 
Citation: Picklo MJ, etal., Brain Res. 2001 Oct 19;916(1-2):229-38.
RGD ID: 14349051
Pubmed: PMID:11597610   (View Abstract at PubMed)

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 gamma-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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
AKR7A2HumanAlzheimer's disease  IEP protein:increased expression:superior and middle temporal gyrusRGD 
Akr7a2RatAlzheimer's disease  ISOAKR7A2 (Homo sapiens)protein:increased expression:superior and middle temporal gyrusRGD 
Akr7a5MouseAlzheimer's disease  ISOAKR7A2 (Homo sapiens)protein:increased expression:superior and middle temporal gyrusRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Akr7a2Ratnuclear envelope  IDA  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Akr7a2  (aldo-keto reductase family 7, member A2)

Genes (Mus musculus)
Akr7a5  (aldo-keto reductase family 7, member A5)

Genes (Homo sapiens)
AKR7A2  (aldo-keto reductase family 7 member A2)


Additional Information