Has resveratrol a potential for mucopolysaccharidosis treatment?

Abstract

Mucopolysaccharidoses (MPS) represent a devastating group of lysosomal storage diseases (LSD) affecting approximately 1 in 25,000 individuals, where degradation of glycosaminoglycans (GAG) by lysosomal enzymes is impaired due to mutations causing defects in one of GAG-degrading enzymes. The most commonly used therapy for MPS is enzyme replacement therapy, consisting of application of an active form of the missing enzyme. However, supply of the missing enzyme is not enough in case of MPS types whose symptoms are expressed in central nervous system (CNS), as enzyme does not cross the blood-brain barrier. Moreover, even though enzyme replacement therapy for non-neuronopathic MPS IVA type is approved, it has a limited impact on bone abnormalities, that are one of main symptoms in the disease. Therefore, research into alternative therapeutic approaches for these types of MPS is highly desirable. One such alternative strategy is accelerated degradation of GAG by induction of autophagy. Autophagy is a process of lysosomal degradation of macromolecules that become abnormal or unnecessary for cells. One of the latest discoveries is that GAGs can also be such molecules. Potential drug should also cross blood-brain barrier and be safe in long-term therapy. It seems that one of the polyphenols, resveratrol, can meet the requirements. The mechanism of its action in autophagy stimulation is pleiotropic. Therefore, in this review, we will briefly discuss potential of resveratrol treatment for mucopolysaccharidosis through autophagy stimulation based on research in diseases with similar outcome.

Keywords: Autophagy; Glycosoaminoglycans; Mucopolysaccharidosis; Trans-Resveratrol.