Decrease in a proenkephalin peptide in cerebrospinal fluid in Huntington's disease and progressive supranuclear palsy

The cerebrospinal fluid (CSF) content of Met5-enkephalin-Arg-Gly-Leu immunoreactivity was found to be significantly decreased in patients with Huntington's disease and progressive supranuclear palsy. This peptide is derived from the proenkephalin precursor protein and normally is found in high concentrations in the basal ganglia. The decrease in CSF from Huntington's disease patients likely reflects the loss of proenkephalin-containing neurons seen in postmortem analyses of basal ganglia tissue. The decrease in progressive supranuclear palsy, a disease in which dopamine neurons degenerate but enkephalin levels in the basal ganglia are reportedly not decreased, may reflect a functional decline in enkephalinergic neuronal activity secondary to a striatal cholinergic deficit. The results suggest that a substantial portion of the CSF Met5-enkephalin-Arg-Gly-Leu immunoreactivity is derived from the basal ganglia and that CSF levels of this peptide can serve as an index of functional or anatomical integrity of proenkephalin synthesizing neurons in the basal ganglia.