The modulation of p75 neurotrophin receptor reduces oxidative stress and inflammation in a cellular model of Rett syndrome

Rett syndrome (RTT) is an early-onset neurological disorder that primarily affects females, causing severe cognitive and physical disabilities. Recently, an imbalance in redox homeostasis and exacerbated inflammatory response have been shown to play a central role in the diverse clinical manifestations of the disease.Numerous studies have highlighted that p75 neurotrophin receptor (p75NTR) may have a role in the regulation of oxidative stress (OS) and inflammation.Therefore, the aim of this work was to evaluate whether the modulation of p75NTR by LM11A-31 counteracts the alterations in OS and inflammation in cultured fibroblasts derived from RTT patients.The main results demonstrate that LM11A-31 reduces the amount of OS markers in RTT fibroblasts. p75NTR modulation by LM11A-31 exerts its antioxidant role by restoring glutathione levels, as well as reducing the expression of the pro-oxidant enzyme Nox4. In addition, LM11A-31 efficiently blunts the expression of pro-inflammatory markers such as interleukin-6 and interleukin-8.Taken together, our data suggest that the modulation of p75NTR may represent an effective therapeutic target to ameliorate the altered redox balance and the inflammation observed in RTT.