RGD Reference Report - SOD1 (copper/zinc superoxide dismutase) deficiency drives amyloid beta protein oligomerization and memory loss in mouse model of Alzheimer disease. - Rat Genome Database

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SOD1 (copper/zinc superoxide dismutase) deficiency drives amyloid beta protein oligomerization and memory loss in mouse model of Alzheimer disease.

Authors: Murakami, K  Murata, N  Noda, Y  Tahara, S  Kaneko, T  Kinoshita, N  Hatsuta, H  Murayama, S  Barnham, KJ  Irie, K  Shirasawa, T  Shimizu, T 
Citation: Murakami K, etal., J Biol Chem. 2011 Dec 30;286(52):44557-68. doi: 10.1074/jbc.M111.279208. Epub 2011 Nov 9.
RGD ID: 8655610
Pubmed: PMID:22072713   (View Abstract at PubMed)
PMCID: PMC3247976   (View Article at PubMed Central)
DOI: DOI:10.1074/jbc.M111.279208   (Journal Full-text)

Oxidative stress is closely linked to the pathogenesis of neurodegeneration. Soluble amyloid beta (Abeta) oligomers cause cognitive impairment and synaptic dysfunction in Alzheimer disease (AD). However, the relationship between oligomers, oxidative stress, and their localization during disease progression is uncertain. Our previous study demonstrated that mice deficient in cytoplasmic copper/zinc superoxide dismutase (CuZn-SOD, SOD1) have features of drusen formation, a hallmark of age-related macular degeneration (Imamura, Y., Noda, S., Hashizume, K., Shinoda, K., Yamaguchi, M., Uchiyama, S., Shimizu, T., Mizushima, Y., Shirasawa, T., and Tsubota, K. (2006) Proc. Natl. Acad. Sci. U.S.A. 103, 11282-11287). Amyloid assembly has been implicated as a common mechanism of plaque and drusen formation. Here, we show that Sod1 deficiency in an amyloid precursor protein-overexpressing mouse model (AD mouse, Tg2576) accelerated Abeta oligomerization and memory impairment as compared with control AD mouse and that these phenomena were basically mediated by oxidative damage. The increased plaque and neuronal inflammation were accompanied by the generation of N(epsilon)-carboxymethyl lysine in advanced glycation end products, a rapid marker of oxidative damage, induced by Sod1 gene-dependent reduction. The Sod1 deletion also caused Tau phosphorylation and the lower levels of synaptophysin. Furthermore, the levels of SOD1 were significantly decreased in human AD patients rather than non-AD age-matched individuals, but mitochondrial SOD (Mn-SOD, SOD2) and extracellular SOD (CuZn-SOD, SOD3) were not. These findings suggest that cytoplasmic superoxide radical plays a critical role in the pathogenesis of AD. Activation of Sod1 may be a therapeutic strategy for the inhibition of AD progression.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Alzheimer's disease  ISOSod1 (Mus musculus)8655610; 8655610 RGD 
Alzheimer's disease  IEP 8655610protein:decreased expression:frontal lobe (human)RGD 
Alzheimer's disease  ISOSOD1 (Homo sapiens)8655610; 8655610protein:decreased expression:frontal lobe (human)RGD 
Alzheimer's disease  IMP 8655610 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Sod1  (superoxide dismutase 1)

Genes (Mus musculus)
Sod1  (superoxide dismutase 1, soluble)

Genes (Homo sapiens)
SOD1  (superoxide dismutase 1)


Additional Information