Phospholipid synthesis is decreased in neuronal tissue in a mouse model of Sandhoff disease

Autor: Buccoliero, R., Bodennec, J., Van Echten-Deckert, G., Sandhoff, K., Futerman, A.H.
Přispěvatelé: Department of Biological Chemistry, Weizmann Institute of Science [Rehovot, Israël], Kekulé-Institut für Organische Chemie und Biochemie, Rheinische Friedrich-Wilhelms-Universität Bonn
Jazyk: angličtina
Rok vydání: 2004
Předmět:
Zdroj: Journal of Neurochemistry
Journal of Neurochemistry, Wiley, 2004, 90, pp.80-88. ⟨10.1111/j.1471-4159.2004.02457.x⟩
ISSN: 0022-3042
1471-4159
Popis: Sandhoff disease is a progressive neurodegenerative disorder caused by mutations in the HEXB gene which encodes for the beta-subunit of beta-hexosaminidase A and B, resulting in ganglioside GM(2) accumulation in the brain. We now demonstrate that phospholipid metabolism is altered in both cultured neurons and in brain tissue from a mouse model of Sandhoff disease, the Hexb-/- mouse. Metabolic labelling using [methyl-(14)C]choline and l-[3-(3)H]serine demonstrated reduced incorporation of [methyl-(14)C]choline into phospholipids in brain tissue but not in liver or spleen. Phospholipid mass was also reduced in brain. The activities of CTP : phosphocholine cytidylyltransferase (CCT) and phosphatidylserine synthase were also reduced in brain tissue from Hexb-/- mice, probably because of post-translational modification as no changes were observed in levels of enzyme expression. The relevance of these findings to Sandhoff disease in human patients is strengthened by observations made over 30 years ago on autopsy tissue of Tay Sachs and Sandhoff disease patients, in which reduced phospholipid levels were observed. We suggest that changes in phospholipid metabolism are not simply because of loss of neuronal tissue as a result of degeneration but rather may cause degeneration, and we discuss the possible effects that changes in phospholipid metabolism could play in the neuropathophysiology of Sandhoff disease.
Databáze: OpenAIRE
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