The role of N-acetylaspartic acid in brain metabolism and the pathogenesis in Canavan disease

The role of N-acetylaspartic acid (NAA) in brain function is not known. The discovery that spongy degeneration of the brain, Canavan disease, is caused by deficiency of aspartoacylase and accumulation of NAA in the brain of these patients has renewed the interest in the metabolism and biological role of NAA in normal brain. NAA is synthesized only in the central nervous system. While NAA is much higher in gray matter compared to white matter, the hydrolytic enzyme aspartoacylase, is present mainly in white matter. It appears that aspartoacylase activity is expressed from early in fetal development and increases in activity with age, particularly in the central nervous system. Despite higher concentration of NAA in the gray matter, the pathology in Canavan disease is observed in the white matter, the site of NAA acid utilization. Further work is required to understand the precise mechanism of the pathology in Canavan disease.