Aspartoacylase is restricted primarily to myelin synthesizing cells in the CNS: therapeutic implications for Canavan disease.
Canavan disease is a devastating neurodegenerative childhood disease caused by mutations in aspartoacylase, an enzyme that deacetylates N-acetylaspartate to generate free acetate in the brain. Localization of aspartoacylase in different cell types in the rat brain was examined in an attempt to understand the pathogenesis of Canavan disease. In situ hybridization histochemistry with a riboprobe based on murine aspartoacylase cDNA was used in this study. The hybridization signal was detectable primarily in the myelin-synthesizing cells, namely oligodendroglia. These findings provide strong additional support for insufficient myelin synthesis as the pathogenic basis of Canavan disease and make a compelling case for acetate supplementation as a simple and noninvasive therapy for this fatal disease with no treatment.
Kirmani
Batool F
BF
Jacobowitz
David M
DM
Kallarakal
Abraham T
AT
Namboodiri
M A A
MA
D019342:Acetic Acid / Q000378:metabolism; D000581:Amidohydrolases / Q000235:genetics*; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D017825:Canavan Disease / Q000188:drug therapy / Q000201:enzymology* / Q000503:physiopathology; D002490:Central Nervous System / Q000201:enzymology* / Q000503:physiopathology; D003593:Cytoplasm / Q000201:enzymology; D008636:Mesencephalon / Q000166:cytology / Q000201:enzymology; D009186:Myelin Sheath / Q000201:enzymology*; D009413:Nerve Fibers, Myelinated / Q000201:enzymology; D009836:Oligodendroglia / Q000201:enzymology*; D016548:Prosencephalon / Q000166:cytology / Q000201:enzymology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012249:Rhombencephalon / Q000166:cytology / Q000201:enzymology
D012333:RNA, Messenger; D001224:Aspartic Acid; C000179:N-acetylaspartate; D000581:Amidohydrolases; C019751:aspartoacylase; D019342:Acetic Acid