The calcium hypothesis of brain aging and neurodegenerative disorders: significance in diabetic neuropathy.
In this paper we discuss the possible role of disturbed neuronal calcium homeostasis in brain aging and diabetic neuropathy. Disturbances in the homeostasis of cytosolic calcium concentration have been implicated in the pathogenesis of various acute and chronic neurodegenerative disorders and in brain aging. Obviously, these disorders do not all share the same pathogenetic mechanisms. However, a number of the pathogenetic mechanisms involved have in common that they may ultimately cause loss of calcium homeostasis, leading to neuronal damage. By identifying the possible role of calcium, treatment strategies can be developed 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 neuropathy, including ischemia, oxidative stress and non-enzymatic protein glycosylation. Each of these factors might impair neuronal calcium homeostasis, and ultimately lead to neurodegenerative changes. By discussing the putative role of these specific factors in two apparently dissimilar disorders, such as brain aging and diabetic neuropathy, we obviously 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 emphasize the importance of disturbances in cellular calcium homeostasis as a final common pathway in neuronal damage resulting from various noxious events.
Biessels
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Rudolf Magnus Institute for Neurosciences, Department of Medical Pharmacology, Utrecht, NL.
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D000375:Aging / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D003929:Diabetic Neuropathies / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D009422:Nervous System Diseases / Q000378:metabolism*; D009473:Neuronal Plasticity
D002118:Calcium