Physiological Features of the Neural Stem Cells Obtained from an Animal Model of Spinal Muscular Atrophy and Their Response to Antioxidant Curcumin

• Published in: International journal of molecular sciences 2024-08, Vol.25 (15), p.8364
• Main Authors: Adami, Raffaella, Pezzotta, Matteo, Cadile, Francesca, Cuniolo, Beatrice, Rovati, Gianenrico, Canepari, Monica, Bottai, Daniele
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants; Antioxidants - pharmacology; Bioavailability; Cell Differentiation - drug effects; Cells, Cultured; curcumin; Curcumin - pharmacology; Disease; Disease Models, Animal; Humans; Medical prognosis; Metabolism; Mice; Motor Neurons - drug effects; Motor Neurons - metabolism; Muscular Atrophy, Spinal - drug therapy; Muscular Atrophy, Spinal - genetics; Muscular Atrophy, Spinal - metabolism; Muscular Atrophy, Spinal - pathology; neural stem cells; Neural Stem Cells - drug effects; Neural Stem Cells - metabolism; neurological disease; NF-E2-Related Factor 2 - genetics; NF-E2-Related Factor 2 - metabolism; NRF2; oxidative stress; Oxidative Stress - drug effects; Patients; Physiological aspects; Physiology; Proteins; spinal muscular atrophy; Stem cells; Transplantation; Young adults
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25158364

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 ( ) . The high heterogeneity of the SMA pathophysiology is determined by the number of copies of , 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.