| Autor: |
Adami R; Section of Pharmacology and Biosciences, Department of Pharmaceutical Sciences, University of Milan, Via Balzaretti 9, 20133 Milan, Italy., Pezzotta M; Section of Pharmacology and Biosciences, Department of Pharmaceutical Sciences, University of Milan, Via Balzaretti 9, 20133 Milan, Italy., Cadile F; Human Physiology Unit, Department of Molecular Medicine, University of Pavia, Via Forlanini 6, 27100 Pavia, Italy., Cuniolo B; Section of Pharmacology and Biosciences, Department of Pharmaceutical Sciences, University of Milan, Via Balzaretti 9, 20133 Milan, Italy., Rovati G; Section of Pharmacology and Biosciences, Department of Pharmaceutical Sciences, University of Milan, Via Balzaretti 9, 20133 Milan, Italy., Canepari M; Human Physiology Unit, Department of Molecular Medicine, University of Pavia, Via Forlanini 6, 27100 Pavia, Italy., Bottai D; Section of Pharmacology and Biosciences, Department of Pharmaceutical Sciences, University of Milan, Via Balzaretti 9, 20133 Milan, Italy. |
| Abstrakt: |
The most prevalent rare genetic disease affecting young individuals is spinal muscular atrophy (SMA), which is caused by a loss-of-function mutation in the telomeric gene survival motor neuron ( SMN ) 1 . The high heterogeneity of the SMA pathophysiology is determined by the number of copies of SMN2 , a separate centromeric gene that can transcribe for the same protein, although it is expressed at a slower rate. SMA affects motor neurons. However, a variety of different tissues and organs may also be affected depending on the severity of the condition. Novel pharmacological treatments, such as Spinraza, Onasemnogene abeparvovec-xioi, and Evrysdi, are considered to be disease modifiers because their use can change the phenotypes of the patients. Since oxidative stress has been reported in SMA-affected cells, we studied the impact of antioxidant therapy on neural stem cells (NSCs) that have the potential to differentiate into motor neurons. Antioxidants can act through various pathways; for example, some of them exert their function through nuclear factor (erythroid-derived 2)-like 2 (NRF2). We found that curcumin is able to induce positive effects in healthy and SMA-affected NSCs by activating the nuclear translocation of NRF2, which may use a different mechanism than canonical redox regulation through the antioxidant-response elements and the production of antioxidant molecules. |
