Chemical chaperones improve peroxisomal biogenesis in fibroblasts of mild Zellweger syndrome spectrum patients

Extract

Zellweger syndrome spectrum (ZSS) disorders are multisystem genetic disorders which lack functional peroxisomes due to a defect in one of the PEX genes. The ZSS include three phenotypes, which represent a spectrum of disease severity with Zellweger syndrome (ZS) being the most severe. In contrast to patients with the ZS phenotype, mild patients can be characterized by very mildly abnormal peroxisomal parameters in cultured skin fibroblasts, including a mosaic catalase immunofluorescence pattern. Such a mosaic pattern is described for specific missense mutations in various PEX genes. Possibly, these missense mutations cause an unstable and/or incorrect folded native state of the protein. We hypothesize that the functional activity of the mutant PEX1 can be enhanced by promoting protein folding with chemical chaperones (e.g. glycerol or arginine) and thereby stimulating peroxisome biogenesis. …