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

Michael Marlatt, Hyoung-gon Lee, George Perry, Mark A Smith, Xiongwei Zhu
2004 Acta Neurobiologiae Experimentalis  
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
more » ... s 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.
pmid:15190682 fatcat:moumbirvc5ayjcmv5sq6vlqdhq