Oxidative Stress in Mucopolysaccharidoses: Pharmacological Implications.

Karolina Pierzynowska,Elisabetta Profumo,Zuzanna Cyske,Luciano Saso,Grzegorz Węgrzyn,Brigitta Buttari,Lidia Gaffke

doi:10.3390/molecules26185616

Karolina Pierzynowska, Elisabetta Profumo + Show 5 more

Open Access

https://doi.org/10.3390/molecules26185616

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Abstract

Although mucopolysaccharidoses (MPS) are caused by mutations in genes coding for enzymes responsible for degradation of glycosaminoglycans, storage of these compounds is crucial but is not the only pathomechanism of these severe, inherited metabolic diseases. Among various factors and processes influencing the course of MPS, oxidative stress appears to be a major one. Oxidative imbalance, occurring in MPS and resulting in increased levels of reactive oxidative species, causes damage of various biomolecules, leading to worsening of symptoms, especially in the central nervous system (but not restricted to this system). A few therapeutic options are available for some types of MPS, including enzyme replacement therapy and hematopoietic stem cell transplantation, however, none of them are fully effective in reducing all symptoms. A possibility that molecules with antioxidative activities might be useful accompanying drugs, administered together with other therapies, is discussed in light of the potential efficacy of MPS treatment.

Highlights

The mucopolysaccharidoses (MPS) are a group of rare genetic diseases, being a subset of lysosomal storage diseases (LSD)
Lack or decreased activity of these enzymes leads to GAG storage in lysosomes that eventually leads to progressive damage to cells, tissues, and various organ systems of the body
Disturbances in oxidative processes may have the following effects: (i) they contribute to neuronal loss [12], (ii) they promote prothrombotic reactions, (iii) they increase the level of oxidized cholesterol, (iv) they cause glomerular damage and renal ischemia, (v) they induce immunological responses and chronic inflammation [13,15], and (vi) they result in mitochondrial dysfunctions [11]

Summary

Introduction

The mucopolysaccharidoses (MPS) are a group of rare genetic diseases, being a subset of lysosomal storage diseases (LSD). The most frequently used therapies for MPS include enzyme replacement therapy (ERT), consisting in delivery of the active form of the missing enzyme to the patient’s organism, and hematopoietic stem cell transplantation used in specific cases under multiple conditions [2,3]. These therapies are available only for some MPS types (I, II, IVA, VI, and VII). We collect the previously described data about oxidative imbalance in MPS and discuss the results of research on the activity of antioxidants in the search for drugs for this disease, used separately or as adjuvants

Oxidative Stress as One of the Mechanisms of MPS Pathogenesis

Enzyme Replacement Therapy and Oxidative Stress in MPS Patients

Compounds with Antioxidant Activities and Their Effects in MPS

Findings

Concluding Remarks