RGD Reference Report - Aberrant expression of NOS isoforms in Alzheimer's disease is structurally related to nitrotyrosine formation. - Rat Genome Database

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Aberrant expression of NOS isoforms in Alzheimer's disease is structurally related to nitrotyrosine formation.

Authors: Lüth, Hans-Joachim  Münch, Gerald  Arendt, Thomas 
Citation: Lüth HJ, etal., Brain Res. 2002 Oct 25;953(1-2):135-43.
RGD ID: 13824978
Pubmed: PMID:12384247   (View Abstract at PubMed)

Various isoforms of the nitric oxide (NO) producing enzyme nitric oxide synthase (NOS) are elevated in Alzheimer's disease (AD) indicating a critical role for NO in the pathomechanism. NO can react with superoxide to generate peroxynitrite, a process referred to as oxidative stress, which is likely to play a role in AD. Peroxynitrite in turn, nitrates tyrosine residues to form nitrotyrosine which can be identified immunohistochemically. To study the potential structural link between the increased synthesis of NO and the deposition of nitrotyrosine in AD, we analyzed the expression of neuronal NOS (nNOS), inducible NOS (iNOS) and endothelial NOS (eNOS) in AD and control brain, and compared the localization with the distribution of nitrotyrosine. Nitrotyrosine was detected in neurons, astrocytes and blood vessels in AD cases. Aberrant expression of nNOS in cortical pyramidal cells was highly co-localized with nitrotyrosine. Furthermore, iNOS and eNOS were highly expressed in astrocytes in AD. In addition, double immunolabeling studies revealed that in these glial cells iNOS and eNOS are co-localized with nitrotyrosine. Therefore, it is suggested that increased expression of all NOS isoforms in astrocytes and neurons contributes to the synthesis of peroxynitrite which leads to generation of nitrotyrosine. In view of the wide range of isoform-specific NOS inhibitors, the determination of the most responsible isoform of NOS for the formation of peroxynitrite in AD could be of therapeutic importance in the treatment of Alzheimer's disease.

RGD Manual Disease Annotations    Click to see Annotation Detail View

Objects Annotated

Genes (Rattus norvegicus)
Nos1  (nitric oxide synthase 1)
Nos2  (nitric oxide synthase 2)
Nos3  (nitric oxide synthase 3)

Genes (Mus musculus)
Nos1  (nitric oxide synthase 1, neuronal)
Nos2  (nitric oxide synthase 2, inducible)
Nos3  (nitric oxide synthase 3, endothelial cell)

Genes (Homo sapiens)
NOS1  (nitric oxide synthase 1)
NOS2  (nitric oxide synthase 2)
NOS3  (nitric oxide synthase 3)


Additional Information