Data di Pubblicazione:
2011
Citazione:
Secondary accumulations of gangliosides in sphingolipidosis / E. Chiricozzi, S. Prioni, V.L. Chigorno, A.E.G. Prinetti, S. Sonnino. - In: JOURNAL OF NEUROCHEMISTRY. - ISSN 0022-3042. - 118:Suppl. 1(2011 Aug 01), pp. 210-210. ((Intervento presentato al 23. convegno Biennal Meeting of ISN/ESN tenutosi a Athens nel 2011 [10.1111/j.1471-4159.2011.07326.x].
Abstract:
Sphingolipid metabolism is deeply deregulated in several
pathologies. This seems to be responsible of neurodegeneration,
in sphingolipidosis. Here, we focus the attention on secondary
alterations of sphingolipid metabolism that have been sporadically
reported in the literature, in some sphingolipidosis.
We present a detailed analysis of the lipid composition in
different tissues from the acid sphingomyelinase-deficient mouse
(ASMKO), the animal model for Niemann-Pick disease type A,
characterized by the accumulation of sphingomyelin (SM). The
animal model of NPD type A, was developed using gene targeting
and embryo transfer techniques.
Results show, together with a general accumulation of SM, an
unexpected tissue specific selection of the accumulated molecular
species of SM, and of GM3 and GM2 gangliosides, that cannot be
solely explained by the lack of sphingomyelinase. We observed the
preferential accumulation of SM molecular species with shorter acyl
chains in the nervous system, but not in extraneural tissues. The
unbalance toward C18/C16-fatty acid containing SM species was
detectable as early as SM accumulation started, and monosialoganglioside
accumulation followed immediately afterwards. These
changes in sphingolipid patterns should thus represent the effect
of secondary biochemical pathways altered as a consequence of a
non-related primary cause. The mechanism underlying these
changes still remains to be elucidated and is probably the result
of changes in the expression and/or activity of more than one single
enzyme, and/or of anomalies in the traffic of the substrate/product
concentrations in multiple cellular compartments. Several pieces of
evidence suggest that altered sphingolipid metabolism results in a
non-physiological plasma membrane composition and organization,
leading to altered plasma membrane-originated signalling pathways
that could be relevant to the onset of cellular damage and of tissue
pathology.
Tipologia IRIS:
01 - Articolo su periodico
Elenco autori:
E. Chiricozzi, S. Prioni, V.L. Chigorno, A.E.G. Prinetti, S. Sonnino
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