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Sources and mechanisms of cytoplasmic oxidative damage in Alzheimer's disease

100%

Marlatt M., Lee H., Perry G., Smith M. A., Zhu X.

issue 1

81-87

While evidence supports a pathogenic and proximal role for oxidative stress in Alzheimer's disease, the causes and consequences of reactive oxygen species that promote oxidative damage have not been directly demonstrated. Co-incident with the reduced energy metabolism during the development of the disease, some of the key mitochondrial enzymes have shown deficient activity in AD neurons, which may lead to increased ROS production. However, we found that oxidative damage occurs primarily within the cytoplasm rather than in mitochondria. Given that SOD activity is increased in AD mitochondria and that metal ions such as iron and copper are enriched in susceptible neurons, we hypothesize that mitochondria, as a source, provide hydrogen peroxide, which, as an intermediate, once in the cytoplasm, will be converted into highly reactive hydroxyl radicals through Fenton reaction in the presence of metal ion and cause damage in cytoplasm.

The role of metabotropic glutamate receptors in Alzheimer's disease

73%

Lee H., Zhu X., O'Neill M. J., Webber K., Casadesus G., Marlatt M., Raina A. K., Perry G., Smith M. A.

issue 1

89-98

While glutamatergic transmission is severely altered by early degeneration of cortico-cortical connections and hippocampal projections in Alzheimer's disease (AD), the role of glutamate receptors in the pathogenesis of AD is not yet defined clearly. Nonetheless, as reviewed here, the topographical distribution of different types of receptors likely contributes to the regional selective nature of neuronal degeneration. In particular, metabotropic glutamate receptors (mGluR) may contribute the pathogenesis of many neurological conditions and also regulate neuronal vulnerability against cytotoxic stress. Thus, we here discuss the possible role of mGluR in the pathogenesis of AD based on the results from other neurodegenerative diseases that may give us clues to solve the mysterious selective neurodegeneration evident in AD.

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2 Acta Neurobiologiae Experimentalis

2 2004

2 Lee H.

2 Marlatt M.

2 Perry G.

2 Smith M. A.

2 Zhu X.

1 Casadesus G.

1 O'Neill M. J.

1 Raina A. K.

1 Webber K.

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Sources and mechanisms of cytoplasmic oxidative damage in Alzheimer's disease

The role of metabotropic glutamate receptors in Alzheimer's disease