Thiamine (vitamin B1) dependent processes are reduced in Alzheimer’s disease. Thiamine deficiency mimics many aspects of Alzheimer’s disease including the reduced glucose metabolism and exaggeration of the plaque and tangle pathology.
Reducing the enzyme KGHDC has widespread consequences on cell and brain function. We postulate this is because it is responsible for post-translation modification of thousands of proteins by succinylation.
Alzheimer’s disease related changes in releasable internal calcium stores as well as in mitochondrial function have been suggested from animal studies and cultured cells from Alzheimer’s disease patients such as fibroblasts, and make good therapeutic targets.
Thiamine (vitamin B1) deficiency (TD) produces a mild, chronic impairment of oxidative metabolism that models the diminished metabolism and reduced activities of the thiamine-dependent mitochondrial enzymes that occur in brain in several common age-related neurodegenerative disorders.
Western blots are used extensively to study post-translational modifications of the α-ketoglutarate dehydrogenase complex (KGDHC). The figure shows the separation of ketoglutarate dehydrogenase complex by blue-native gel.