The neuronal ceroid-lipofuscinoses (NCLs) are inherited neurodegenerative diseases. They are believed to be the most common storage disorders affecting humans, with an estimated combined incidence, for all forms, of one case in 12,500 [Rider, 1988]. With intensive supportive therapy, many patients live for several years so that the cost is high, both in human and economic terms. There are several forms in humans. They differ in age of onset~ chromosomal map position and pathology. We are using proteomic analysis for the detection of mutations and for characterisation of a variety of disease processes. Two-dimensional polyacrylamide gel electrophoresis is being used to separate proteins from a range of organs and subcellular fractions prepared from control and affected individuals. We have shown that a few proteins, vary in a disease related manner. Some of these proteins have been identified by microsequencing tryptic fragments of spots excised from the two-dimensional gels, but the abundances of the other variant proteins are too low for this approach. Peptide mass fingerprinting will be used to identify these proteins so that their roles in the disease processes can be ftu-ther examined. Most of the detected protein changes involve increases in abundance in affected animals. Some of these changes may therefore reflect responses to tissue damage. However two unidentified proteins, one apparently mitochondrial and the other apparently lysosomal, show several fold decreases in abundance that might reflect altered expression of a mutant gene in affected tissues.
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