Oxidative Stress in Mucopolysaccharidoses: Pharmacological Implications

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.

Mechanism of Aspirin oxidative stress regulating interleukin-induced apoptosis in nucleus pulposus cells in a rat model of intervertebral disc degeneration

“…Adenosine monophosphate (AMP) -activated protein kinase (AMPK) is an important regulator of cellular energy; AMPK activation helps to correct energy metabolism disorders. In response to cellular stress, AMPK can inhibit the expression of ROS by inducing endogenous antioxidant substances (11)(12)(13). Considering that ROS can directly participate in inflammation, autophagy, apoptosis, and other pathophysiological processes, AMPK activation may help to alleviate the above pathological processes.…”

Redox Imbalance in Neurological Disorders in Adults and Children

“…Increased astrogliosis was observed in autopsies of patients and in a murine model, while microglia and T-cells have never been thoroughly investigated [ 261 , 262 , 263 ]. Studies have shown abnormalities in immune organs (e.g., spleen) and T-cell alterations in SMA mouse models, resulting in an abnormal neuroinflammatory response and exacerbation of the disease [ 264 ]. Importantly, functional studies investigating the status of T-cells and their protective or cytotoxic function in SMA may provide us insight on neuroinflammation in the pathogenesis of SMA.…”

The Inflammation in the Cytopathology of Patients With Mucopolysaccharidoses- Immunomodulatory Drugs as an Approach to Therapy

“…Unfolded protein response (UPR) and consecutive endoplasmatic reticulum (ER) stress may further contribute to cell disruption (Filippon et al, 2011;Pierzynowska et al, 2021).…”