Kurzfassung

Cystinosis is a rare genetic disorder that causes an accumulation of the amino acid cystine within cells, forming crystals that can build up and damage the cells. It is due to a mutation in the gene CTNS which codes for the lysosomal cystine transporter. The aminothiol cysteamine represents the only treatment of cystinotic patients to date. In the lysosomal lumen, cysteamine reacts with cystine to form a cysteine-cysteamine conjugate that (because of its structural similarity to lysine)...Cystinosis is a rare genetic disorder that causes an accumulation of the amino acid cystine within cells, forming crystals that can build up and damage the cells. It is due to a mutation in the gene CTNS which codes for the lysosomal cystine transporter. The aminothiol cysteamine represents the only treatment of cystinotic patients to date. In the lysosomal lumen, cysteamine reacts with cystine to form a cysteine-cysteamine conjugate that (because of its structural similarity to lysine) leaves lysosomes through a transporter selective for cationic amino acids. The latter is known biochemically as lysosomal ‘system c’, but remains unknown at the molecular level. It represents a ‘salvage pathway’ which by-passes the need for a functional cystine transporter.

In this project, we aim at identifying system c at the molecular level and developing a screening system for sulfhydryl compounds that act on cystinotic cells at lower concentration than cysteamine, thus providing a rationale approach to reduce the side-effects and constraints of the cysteamine treatment (gastrointestinal distress, administration every 6 hours).
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