Chaperone Therapy for GM2 Gangliosidosis: Effects of Pyrimethamine on β-Hexosaminidase Activity in Sandhoff Fibroblasts
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- 作者：Elena Chiricozzi ; Natalia Niemir ; Massimo Aureli…
- 关键词：GM2 ; gangliosidosis ; Sandhoff disease ; β ; hexosaminidase ; Pharmacological Chaperone ; Pyrimethamine ; Cultured fibroblasts
- 刊名：Molecular Neurobiology
- 出版年：2014
- 出版时间：August 2014
- 年：2014
- 卷：50
- 期：1
- 页码：159-167
- 全文大小：376 KB
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Natalia Niemir (2)
Massimo Aureli (1)
Alessandro Magini (3)
Nicoletta Loberto (1)
Alessandro Prinetti (1)
Rosaria Bassi (1)
Alice Polchi (3)
Carla Emiliani (3)
Catherine Caillaud (2) (4)
Sandro Sonnino (1)
1. Department of Medical Biotechnology and Translational Medicine, University of Milano, Via F.lli Cervi 93, 20090, Segrate, Italy
2. Sorbonne Paris Cité, Faculté de Médecine Necker, INSERM U845, Université Paris Descartes, Paris, France
3. Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy
4. Service de Biochimie et Génétique Moléculaire, Groupe Hospitalier Cochin-Broca-Hotel Dieu, Assistance Publique-H?pitaux de Paris, Paris, France - ISSN：1559-1182
文摘
Sphingolipidoses are inherited genetic diseases due to mutations in genes encoding proteins involved in the lysosomal catabolism of sphingolipids. Despite a low incidence of each individual disease, altogether, the number of patients involved is relatively high and resolutive approaches for treatment are still lacking. The chaperone therapy is one of the latest pharmacological approaches to these storage diseases. This therapy allows the mutated protein to escape its natural removal and to increase its quantity in lysosomes, thus partially restoring the metabolic functions. Sandhoff disease is an autosomal recessive inherited disorder resulting from β-hexosaminidase deficiency and characterized by large accumulation of GM2 ganglioside in brain. No enzymatic replacement therapy is currently available, and the use of inhibitors of glycosphingolipid biosynthesis for substrate reduction therapy, although very promising, is associated with serious side effects. The chaperone pyrimethamine has been proposed as a very promising drug in those cases characterized by a residual enzyme activity. In this review, we report the effect of pyrimethamine on the recovery of β-hexosaminidase activity in cultured fibroblasts from Sandhoff patients.