Apparent cathepsin B deficiency in neuronal ceroid lipofuscinosis can be explained by peroxide inhibition.

Fibroblasts from patients with various forms of neuronal ceroid lipofuscinosis (NCL or Batten's disease) showed decreasing cathepsin B activity with increasing passage number and time in culture. In contrast, other lysosomal hydrolase activities were largely unaffected. Cathepsin B activity, was found to be associated with the lysosome-enriched fraction following cell disruption and Percoll gradient fractionation. Exposure of fibroblasts to low concentrations (less than 0.1 mM) of hydrogen peroxide either in vivo or in vitro resulted in a dose-dependent loss of cathepsin B activity with no concomitant loss in cathepsin H activity or lysosomal hydrolase activity. These results suggest that a primary defect resulting in accumulation of abnormal peroxides could produce a secondary cathepsin B inhibition in lysosomes and lead to observed peptide and dolichol accumulation in NCL.