Neuronal ubiquitin and neurofilament expression in different lysosomal storage disorders

We studied various lysosomal storage disorders such as Tay-Sachs' disease, Niemann-Pick's disease, and Hunter's disease for their immunoreactivity with antibodies against ubiquitin (Ub) and neurofilaments (NF). We found that in all cases, irrespective of the nature of the storage material or disorder, only a minor proportion of neurons (20-30% at most), as a rule, moderately reacted with the Ub antibody, while the majority of the distended neurons neither expressed Ub nor NF epitopes. These findings suggest that the UB dependent proteolytic pathway may play a secondary role in the lysosomal storage disorders, at least in the advanced stages which are observed at autopsy. It seems that the Ub expression of a minor proportion of neurons should be regarded as an unspecific epiphenomenon rather than as a mechanism of major significance in the basic metabolism of these disorders, in which the inclusions consist of membrane-bound lipid material.