Calcium Homeostasis and Free Radical Metabolism as Convergence Points in the Pathophysiology of Dementia

摘要: Realization that calcium and free radicals are key mediators of neuronal injury death initially came from studies acute neurodegenerative insults, such as ischemia or excitotoxic (see refs. 1 2 for review). At time, many were skeptical (and some remain so) regarding the relevance ischemic to disorders Alzheimer’s disease (AD). Nevertheless, it is becoming increasingly appreciated “final common pathways” cell very similar in both chronic conditions. Central final pathways radicals, which can be considered transducers There also existed somewhat a dichotomy among researchers focusing on mechanisms “necrotic” “apoptotic” death, wherein “apoptologists” believed there fundamental mechanistic differences distinguished apoptosis necrosis. That is, was process cellular suicide involving induction expression “cell genes,” whereas necrosis passive resulting an uncontrollable avalanche ion influx lysis ref. 3 However, more studied, evident became apoptosis, distinction between two manifestations depended quantity (severity duration insult) than quality insult. It therefore critical we understand various genetic environmental factors influence neural homeostasis radical metabolism. This translates into following tacks investigation: 1. Determining how mutations linked specific impact regulation metabolism; 2. Identifying may compromise promote accumulation, determining molecular cascades involved; and 3. Elucidating whereby brain normally resists degeneration (e.g., neurotrophic factor signal transduction response pathways).