Browsing by Author "Gonçalves, Raquel da Fonseca"
Now showing 1 - 1 of 1
Results Per Page
Sort Options
- The effect of chaperone compounds on glucocerebrosidase stability and activity in fibroblasts from Gaucher Disease patients with different genotypesPublication . Gonçalves, Raquel da Fonseca; Tiscórnia, GustavoGaucher disease is the most common lysosomal storage disorder and may present systemic and neurological symptoms. It is caused by mutations in the GBA gene that encodes for glucocerebrosidase (GBA), an enzyme involved in the degradation of sphingolipids in the lysosome of cells. The enzymatic deficiency leads to accumulation of GBA substrate in cell lysosomes. The disease can present three different clinical types: type 1 presents mainly non-‐neuropathic symptoms in multiple organs, whereas type 2 and type 3 are characterized by neurological complications. The only treatments currently available (enzyme replacement therapy and substrate reduction therapy) treat the visceral symptoms, but not the neuropathic manifestations. An alternative approach uses pharmacological chaperones to improve the affected enzyme activity and restore normal activity. This therapy has the potential to treat both neurological and visceral symptoms. The main purpose of this thesis is to test the effect of 8 different chaperone compounds on glucocerebrosidase stability and activity. These chaperones were tested in fibroblasts from Gaucher disease patients with 4 different genotypes. The results on this experimental work suggest that the effect of a given chaperone depends on the mutation affecting the GBA protein. The techniques established in this work will eventually be used to test the effect of chaperone compounds on neurons derived from induced pluripotent stem cells (IPSc) of Gaucher Disease patients, as potential therapeutic agents.