Galactosemia: Towards Pharmacological Chaperones

摘要: Galactosemia is a rare inherited metabolic disease resulting from mutations in the four genes which encode enzymes involved metabolism of galactose. The current therapy, removal galactose diet, inadequate. Consequently, many patients suffer lifelong physical and cognitive disability. phenotype varies almost asymptomatic to life-threatening fundamental biochemical cause decrease enzymatic activity due failure affected protein fold and/or function correctly. Many novel therapies have been proposed for treatment galactosemia. Often, these are designed treat symptoms not cause. Pharmacological chaperones (PC) (small molecules correct folding misfolded proteins) represent an exciting potential therapy In theory, they would restore enzyme function, thus preventing downstream pathological consequences. practice, no PCs identified application Here, we review basis disease, identify opportunities describe how might be discovered. We will conclude by considering some clinical issues affect future use