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SOD2 and Alzheimer Disease

 

 

SOD2

Superoxide dismutase 2 (SOD2) is a manganese SOD which acts in the mitochondria to convert superoxide free radicals to peroxide (Lethem and Orrell 1997).  Superoxide free radicals have found to mediate Aβ42 toxicity to neurons and vascular vessels (Suo et al. 1997).  Serum concentrations of SOD2 are found to be significantly reduced in AD patients (Thome et al. 1997), while SOD2 is found in the senile plaques of AD patients and could be associated with their formation (Maeda et al. 1997).  SOD2 has been found to be induced by inflammatory cytokines, dietary fat excluding fish oil, and increases in free radical levels (Kuratko and Constante 1998). 

In transgenic mice, overexpression of SOD2 provides protection against attack by free radicals.  However, SOD2 knockout mice produced at Baylor died prematurely, had abnormal behavior, and showed degeneration of their brain neurons (Przedborski and Schon 1998).  Melov et al. (1998) examined SOD2 knockout mice that died prematurely with metabolic and mitochondrial defects, as well as a spongiform neurodegenerative disorder.  They then treated the mice with a synthetic SOD2 catalase, which extended their lifespan, rescued the spongiform disorder, and attenuated their mitochondrial defects (Melov et al. 2001).  The authors also suggest that this catalase may be a potential AD treatment.

 

Congratulations!  You have discovered a gene that may be linked to Alzheimer Disease.  You have now completed the gene mapping workshop.

 

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References

Kuratko, C. N., and B. J. Constante.  1998.  Linoleic acid and tumor necrosis factor-a increase manganese superoxide dismutase activity in intestinal cells.  Cancer Let  130:191-196.

Lethem, R., and M. Orrell.  1997.  Antioxidants and dementia.  Lancet  349:1189-1190.

Maeda, M., H. Takagi, H. Hattori, and T. Matsuzaki.  1997.  Localization of manganese superoxide

                dismutase in the cerebral cortex and hippocampus of Alzheimer-type senile dementia.  Osaka

                City Med J  43(1):1-5.

Melov S, Schneider JA, Day BJ, Hinerfeld D, Coskun P, Mirra SS, Crapo JD, Wallace DC. 1998.  A novel

                neurological phenotype in mice lacking mitochondrial manganese superoxide dismutase.  Nat 

                Genet 18(2):159-63.

Melov S, Doctrow SR, Schneider JA, Haberson J, Patel M, Coskum PE, Huffman, K, Wallace DC,    

               Malfroy B. 2001.  Lifespan extension and rescue of spongiform encephalopathy in

               superoxide dismutatse 2 nullizygous mice treated with superoxide dismutase-catalase mimetics. 

               J  Neurosci 21:8348-8353.

Przedborski, S., and E. A. Schon.  1998.  Loss of ROS - a radical response.  Nat. Genet.  18:99-100.

Suo, Z., C. Fang, F. Crawford, and M. Mullan.  1997.  Superoxide free radical and intracellular calcium mediate Ab1-42 induced endothelial toxicity.  Brain Res.  762:144-152.

Thome, J., W. Gsell, M. Rosler, J. Kornhuber, L. Frolich, E. Hashimoto, B. Zielke, G. A. Wiesbeck, and P.

               Riederer.  1997.  Oxidative-stress associated parameters (lactoferrin, superoxide dismutases) in

               serum of  patients with Alzheimer's disease.  Life Sci.  60(1):13-19.