Sneak peak at galactocerebrosidase, Krabbe disease's lysosomal hydrolase

Lieberman, Raquel L.

doi:10.1073/pnas.1112653108

Cited by 4 publications

(1 citation statement)

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“…This result was justified given the mutation type. In fact, among the analyzed mutations, the D528N mutation creates a novel glycosylation site and alters protein processing (Lieberman, ), as demonstrated by an increase in GALC activity and processing both after reversing the hyperglycosylation site and during tests under reduced temperature.…”

Section: Chaperones For Kd: Preclinical Studiesmentioning

confidence: 99%

Chaperones as potential therapeutics for Krabbe disease

Graziano

Pannuzzo

Avola

et al. 2016

J of Neuroscience Research

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Krabbe's disease (KD) is an autosomal recessive, neurodegenerative disorder. It is classified among the lysosomal storage diseases (LSDs). It was first described in , but the genetic defect for the galactocerebrosidase (GALC) gene was not discovered until the beginning of the 1970s, 20 years before the GALC cloning. Recently, in 2011, the crystal structures of the GALC enzyme and the GALC-product complex were obtained. For this, compared with other LSDs, the research on possible therapeutic interventions is much more recent. Thus, it is not surprising that some treatment options are still under preclinical investigation, whereas their relevance for other pathologies of the same group has already been tested in clinical studies. This is specifically the case for pharmacological chaperone therapy (PCT), a promising strategy for selectively correcting defective protein folding and trafficking and for enhancing enzyme activity by small molecules. These compounds bind directly to a partially folded biosynthetic intermediate, stabilize the protein, and allow completion of the folding process to yield a functional protein. Here, we review the chaperones that have demonstrated potential therapeutics during preclinical studies for KD, underscoring the requirement to invigorate research for KD-addressed PCT that will benefit from recent insights into the molecular understanding of GALC structure, drug design, and development in cellular models. © 2016 Wiley Periodicals, Inc.

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Section: Chaperones For Kd: Preclinical Studiesmentioning

confidence: 99%