THE CALCIUM HYPOTHESIS OF BRAIN AGING AND NEURODEGENERATIVE DISORDERS- SIGNIFICANCE IN DIABETIC NEUROPATHY

In this paper we discuss the possible role of disturbed neuronal calci um homeostasis in brain aging and diabetic neuropathy. Disturbances in the homeostasis of cytosolic calcium. concentration have been implica ted in the pathogenesis of various acute and chronic neurodegenerative disorders and in brain aging. Obviously, these disorders do not all s hare the same pathogenetic mechanisms. However, a number of the pathog enetic mechanisms involved have in common that they may ultimately cau se loss of calcium homeostasis, leading to neuronal damage. By identif ying the possible role of calcium, treatment strategies can be develop ed that may be effective in a variety of neurodegenerative disorders, despite differences in their pathogenesis. Our aim is to explore some of the similarities that exist between a number of processes that have been implicated in the pathogenesis of brain aging and diabetic neuro pathy, including ischemia, oxidative stress and non-enzymatic protein glycosylation. Each of these factors might impair neuronal calcium hom eostasis, and ultimately lead to neurodegenerative changes. By discuss ing the putative role of these specific factors in two apparently diss imilar disorders, such as brain aging and diabetic neuropathy, we obvi ously do not intend to suggest that their pathogenesis is one and the same. Instead, by examining the relative role of these factors in two different types of neurodegenerative disorders we would like to emphas ize the importance of disturbances in cellular calcium homeostasis as a final common pathway in neuronal damage resulting from various noxio us events.