Putative adjunct therapies to target mitochondrial dysfunction and oxidative stress in phenylketonuria, lysosomal storage disorders and peroxisomal disorders

Abstract

ABSTRACT Introduction: Oxidative stress (OS) and mitochondrial dysfunction are implicated in the pathogenesis of a number of metabolic diseases. OS occurs when there is an imbalance between the pro-oxidant/antioxidant homeostasis, leading to an increased generation of reactive oxidant species (ROS) with resultant cellular dysfunction. It is becoming apparent that increased ROS generation may be attributable to secondary mitochondrial dysfunction as a consequence of disease pathophysiology. Mitochondrial dysfunction occurs as a result of oxidative damage from enhanced ROS generation as well as the accumulation of toxic metabolites in some metabolic diseases. Areas covered: The present review will discuss evidence of OS and mitochondrial dysfunction in phenylketonuria (PKU), lysosomal storage disorders (LSDs), and peroxisomal disorders. In addition, potential adjunct therapies which have the potential to enhance mitochondrial functioning and mitigate OS will be explored. The databases utilized for this review were Pubmed and the Wed of science, with inclusive dates, 1988–2020. Expert opinion: There is an un-unified approach in the treatment of metabolic diseases. Agents including augmenters of mitochondrial function, antioxidants, and activators of mitochondrial biogenesis, may be beneficial. However, although successful in some cases, these adjunct therapies have yet to be incorporated into the clinical-management of metabolic diseases.