4-Phenylbutyrate rescues trafficking incompetent mutant alpha-galactosidase A without restoring its functionality
- PMID: 17592721
- DOI: 10.1016/j.bbrc.2007.06.048
4-Phenylbutyrate rescues trafficking incompetent mutant alpha-galactosidase A without restoring its functionality
Abstract
Fabry disease is a lysosomal storage disorder caused by deficiency of alpha-galactosidase A. Most mutant enzyme is catalytically active but due to misfolding retained in the endoplasmic reticulum. We have tested 4-phenylbutyrate for its potential to rescue various trafficking incompetent mutant alpha-galactosidase A. Although we found that the trafficking blockade for endoplasmic reticulum-retained mutant alpha-Gal A was released, neither a mature enzyme was detectable in transgenic mice fibroblasts nor a reversal of lysosomal Gb3 storage in fibroblasts from Fabry patients could be observed. Because of lack of functionality of rescued mutant alpha-galactosidase A, 4-phenylbutyrate seems to be of limited use as a chemical chaperone for Fabry disease.
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