Hexosaminidases and ganglioside catabolism in the GM2-gangliosidoses

Abstract The G M2 -gangliosidoses are a set of neurological diseases whose common features include the storage of the ganglioside G M2 , N-acetyl galactosaminyl (N-acetylneuraminyl-) galactosylglucosylceramide and related neutral glycosphingolipids in various organs (particularly brain) of affected individuals and the inability of such individuals' hexosaminidases to catalyze the hydrolysis of G M2 . Associated with this finding has been the demonstration of a deficiency in none, one or both major forms (A and B) of hexosaminidase which can be measured with artificial flurogenic or chromogenic substrates. Additionally, a deficiency in the A form of hexosaminidase which is usually associated with Tay-Sachs disease has been demonstrated in certain clinically normal adults. Recent advances in the purification of the two forms of hexosaminidase have allowed their catalytic, immunological, physical and genetic characteristics to be examined in great detail. This examination has resulted in the proposal of several models for the relationship of the hexosaminidases and their involvment in the G M2 -gangliosidoses. I discuss the evidence for these models and the implications which can be drawn from them in this review.