Glycosphingolipid patterns and glycohydrolases behavior in acid-sphingomyelinase knock-out mice
Abstract
Data di Pubblicazione:
2013
Citazione:
Glycosphingolipid patterns and glycohydrolases behavior in acid-sphingomyelinase knock-out mice / S. Prioni, M. Aureli, N. Loberto, R. Bassi, V. Murdica, M. Samarani, E. Chiricozzi, E. Chigorno, S. Sonnino, A. Prinetti. - In: JOURNAL OF NEUROCHEMISTRY. - ISSN 0022-3042. - 125:suppl. 1(2013), pp. 251-251. ((Intervento presentato al 24. convegno Biennial Meeting of the International Society for Neurochemistry and the American Society for Neurochemistry (ISN/ASN) tenutosi a Cancun nel 2013.
Abstract:
Niemann-Pick type A (NPA) disease is a lysosomal storage
disorder caused by a deficiency in the enzyme acid sphingomyelinase
(ASMase). This inherited sphingolipidosis is characterized by
a rapidly progressive neurodegenerative course.
It is now known that secondary to sphingomyelin storage, other
lipids, including gangliosides, also accumulate in NPA patients,
leading to many cellular abnormalities. In particular we found that
the lipid composition of different central nervous system and
extraneural tissues from the acid sphingomyelinase-deficient mouse
(ASMKO), the animal model for Niemann-Pick disease type A, is
characterized by an unexpected, tissue specific selection of the
accumulated molecular species of sphingomyelin, and an accumulation
of GM3 and GM2 gangliosides in both neural and extraneural
tissues, that cannot be solely explained by the lack of acid
sphingomyelinase. On these bases, we determine the glycohydrolytic
enzyme panel in ASMKO mice as experimental model. The
activity of different glycohydrolases was measured in the homogenates
of brain, cerebellum, liver, spleen and testis from male mice
at 1.5, 3 and 6 months. In particular, b-glucosidase GBA1, GBA2,
b-galactosidase, b-hexosaminidase and Neu3 sialidase were evaluated.
The data obtained revealed that the activity of most of the
enzymes increased with the age in the majority of the organs
analyzed in both wild type and ASMKO mice. b-glucosidase GBA1
and b-hexosaminidase activities were significantly higher in ASMKO
animals than in control mice. Remarkably, such increase in the
activity of both the enzymes was already detectable at the first age
considered. In addition, an increase in the activity of b-galactosidase
and Neu3 was also detectable in ASKMO mice at 6 months when
compared to wild type animals of the same age.
These results suggest that the activity of several glycohydrolases
is markedly altered in ASMKO mice, suggesting a possible role for
some of these enzymes as earlier markers of NPA disease. In
particular, GBA1 seems to represent a good candidate to be
exploited for diagnostic and/or prognostic purposes.
Tipologia IRIS:
01 - Articolo su periodico
Elenco autori:
S. Prioni, M. Aureli, N. Loberto, R. Bassi, V. Murdica, M. Samarani, E. Chiricozzi, E. Chigorno, S. Sonnino, A. Prinetti
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