Joseph disease is an autosomal-dominant,
spinocerebellar degeneration characterized at the biochemical level by elevations in the steady-state levels of several abundant
proteins (H, J, and L) in affected brain areas such as the cerebellar cortex. The increased levels of these
proteins could either be a consequence of a relative increase in their de novo synthesis or result from altered rates of proteolysis in degenerating brain cells. These alternatives can be distinguished by comparing the in vitro
protein-synthetic capacities of the messenger
ribonucleic acid populations isolated from cerebellar cortex of control subjects and patients with
Joseph disease.
Protein H (
glial fibrillary acidic protein) is synthesized at detectable levels by all messenger
ribonucleic acid isolates, and the levels of its translatable messenger
ribonucleic acid are reproducibly increased in
ribonucleic acids isolated from cerebellar cortex of patients with
Joseph disease as compared with those isolated from cerebellar cortex of control subjects. Thus, the increased level of
protein H in
Joseph disease is a consequence of an increase in its de novo synthesis and is correlated with the increased number of cerebellar glial cells. In contrast to these results, there is no detectable synthesis of
proteins J and L by messenger
ribonucleic acid populations isolated from cerebellar cortex of either
Joseph disease patients or control subjects, suggesting that the increased levels of these
proteins in affected cerebellar cortex are a consequence of posttranslational
protein modifications.