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Neural precursor cell cultures from GM2 gangliosidosis animal models recapitulate the biochemical and molecular hallmarks of the brain pathology
Author(s) -
Martino Sabata,
Di Girolamo Ilaria,
Cavazzin Chiara,
Tiribuzi Roberto,
Galli Rossella,
Rivaroli Anna,
Valsecchi Manuela,
Sandhoff Konrad,
Sonnino Sandro,
Vescovi Angelo,
Gritti Angela,
Orlacchio Aldo
Publication year - 2009
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2009.05919.x
Subject(s) - gangliosidosis , biology , sandhoff disease , ganglioside , embryonic stem cell , hexosaminidase , sialidase , microbiology and biotechnology , in vitro , cell culture , biochemistry , enzyme , gene , genetics , neuraminidase
In this work we showed that genotype‐related patterns of hexosaminidase activity, isoenzyme composition, gene expression and ganglioside metabolism observed during embryonic and postnatal brain development are recapitulated during the progressive stages of neural precursor cell (NPC) differentiation to mature glia and neurons in vitro . Further, by comparing NPCs and their differentiated progeny established from Tay‐Sachs (TS) and Sandhoff (SD) animal models with the wild‐type counterparts, we studied the events linking the accumulation of undegraded substrates to hexosaminidase activity. We showed that similarly to what observed in brain tissues in TS NPCs and progeny, the stored GM2 was partially converted by sialidase to GA2, which can be then degraded in the lysosomes to its components. The latter can be used in a salvage pathway for the formation of GM3. Interestingly, results obtained from ganglioside feeding assays and from measurement of lysosomal sialidase activity suggest that a similar pathway might work also in the SD model.