Investigating Molecular Mechanisms Underlying Dose-Effect of Gold nanoclusters (Au8-pXs) in Friedreich Ataxia Patients (NanoHealth)
ProjectGold based nanomaterials are applicable to medical imaging, clinica diagnosis methods and therapeutics because of their high versatility, chemical, physical properties, and unique optical characteristics. Our previous studies have demostrated the scaveneger ROS capacity of Au8-pX gold quantum cluster in reducing ROS accumulation and preventing cell death, and in vivio that treatment with Au8-pX mitigates the progression of FRDA-pathology.
Our previous results demonstrated that Au8-pX treatment reach cellular compartments and enter mitochondria supporting a greater antioxidant response. Improvements of the mitochondrial fusion dynamics were also observed as well as an Au8-pXs mediated FXN production in FRDA bone marrow-derived mesenchymal stem cells, suggesting an indirect role in regulating FXN expression.
In this study, FRDA patient’s lymphocytes derived from peripheral blood will be characterized from a metabolic point of view for the dose-dependent effects of Au8-pXs on FXN recovery, and on mitochondrial activity and autophagic flux severely impaired because of oxidative damage. iPSCs derived from fibroblasts isolated from FRDA patients will be differentiated into the clinically relevant model of neurons and therapeutic response to Au8-pX treatment will be evaluated to determine specific and beneficial molecular pathway and bias to be overcome.
Main goal of this project is to achieve knowledge of therapeutic targets of Au8-pXs and simultaneously address inter and intra-variability of Au8-pXs in FRDA cell response to move further future clinical traits.
Our previous results demonstrated that Au8-pX treatment reach cellular compartments and enter mitochondria supporting a greater antioxidant response. Improvements of the mitochondrial fusion dynamics were also observed as well as an Au8-pXs mediated FXN production in FRDA bone marrow-derived mesenchymal stem cells, suggesting an indirect role in regulating FXN expression.
In this study, FRDA patient’s lymphocytes derived from peripheral blood will be characterized from a metabolic point of view for the dose-dependent effects of Au8-pXs on FXN recovery, and on mitochondrial activity and autophagic flux severely impaired because of oxidative damage. iPSCs derived from fibroblasts isolated from FRDA patients will be differentiated into the clinically relevant model of neurons and therapeutic response to Au8-pX treatment will be evaluated to determine specific and beneficial molecular pathway and bias to be overcome.
Main goal of this project is to achieve knowledge of therapeutic targets of Au8-pXs and simultaneously address inter and intra-variability of Au8-pXs in FRDA cell response to move further future clinical traits.