Interactions of oxidative stress with cellular calcium dynamics and glucose metabolism in Alzheimer's disease

Considerable evidence suggests that oxidative stress (elevated levels of reactive oxygen species), altered energy metabolism, and changes in calcium dynamics are central to Alzheimer's disease (AD). Abnormalities in each Of these processes occur in AD, and they can be plausibly linked to the pathology and clinical outcome of the disease. Abnormalities in these same processes in peripheral tissues, such as fibroblasts, indicate that these are inherent properties of AD cells and Lire not merely a secondary response to neurodegeneration. Results in cultured cells including fibroblasts demonstrate that oxidative stress can lead to the AD-related changes in calcium and energy metabolism. Data also suggest that abnormalities in the cellular calcium stores, the ability to handle oxidative stress, and to respond to metabolic impairment link the AD-causing gene mutations to the disease process. Abnormal metabolism and oxidative stress alter the proteins and cellular processes that are modified in AD, and can be readily linked to neuronal death and brain dysfunction. Prevention and/or correction of these abnormalities are appropriate therapeutic targets. (C) 2002 Elsevier Science Inc.