Neural precursor cell cultures from GM2 gangliosidosis animal models recapitulate the biochemical and molecular hallmarks of the brain pathology

Sabata Martino, Ilaria Di Girolamo, Chiara Cavazzin, Roberto Tiribuzi, Rossella Galli, Anna Rivaroli, Manuela Valsecchi, Konrad Sandhoff, Sandro Sonnino, Angelo Vescovi, Angela Gritti, Aldo Orlacchio

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)135-147
Number of pages13
JournalJournal of Neurochemistry
Volume109
Issue number1
DOIs
Publication statusPublished - Apr 2009

Keywords

  • Brain development
  • Lysosomal enzymes
  • Neural precursor cells
  • Sandhoff
  • Tay-Sachs

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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