Altered protein patterns in brains of children with neuronal ceroid lipofuscinosis.

The neuronal ceroid lipofuscinoses (NCL) are a group of inherited neurodegenerative diseases characterized by massive intralysosomal accumulation of storage materials. We have studied the protein patterns in 5 NCL, 5 control, and one Alzheimer disease brains. When protein patterns in NCL and control brain gray matter homogenates were examined by SDS-PAGE, NCL brains showed an absence or greatly reduced amounts of the Mr 160-180 kDa component and reduced amounts of the Mr 29-36 kDa component. Concomitantly, an increase in several components with Mrs of 45-50 kDa was noted. The 180 kDa polypeptide appears to be a glycoprotein because it was bound to the lectins concanavalin A and Ulex europaeus. Recently, the abnormal processing of amyloid protein precursor (APP) and its potential role in NCL have been suggested. Possible defects in tissue proteases and protease inhibitors may be considered responsible for the presence of these amyloid beta protein precursor fragments. To examine this possibility we are using polyclonal antibodies to the C terminal 672-695 (APP) and monoclonal antibodies to inter-alpha-trypsin inhibitor. Polypeptides with molecular weights of approximately 35-38 kDa were detected in the NCL brain, but not in controls in both cases. These findings suggest abnormal protein processing in NCL brain tissue, disturbances in protein and glycoconjugate metabolism, impaired lysosomal function (i.e., metabolic enzyme and/or proteases/proteinase inhibitor abnormalities), and the involvement of improperly processed APP.