Targeting p75NTR activity alleviates the neurotoxic effect of high glucose on iPSC-derived dopaminergic neurons.
Konstantina Chanoumidou, Ioanna Zota, Maria Anna Papadopoulou, Chrystalla Konstantinou, Alexandros Tsimpolis, Electra Tsagliotis, Maria Tziortziou, Katerina Ntarntani, Anne Grünewald, Matthieu David Lavigne, Achille Gravanis, Ioannis Charalampopoulos
Abstract
Hyperglycemia, a hallmark of diabetes mellitus, is a metabolic condition that highly affects the nervous system. While evidence from epidemiological and animal studies links diabetes to dopaminergic dysfunction and an increased risk of Parkinson's disease, the underlying mechanisms remain unclear. Here, we examined the effects of high glucose on human iPSC-derived dopaminergic neurons and glial cells to better understand the pathogenic alterations that lead to neurotoxicity. Previous implication of neurotrophins in the neurological manifestations of diabetes prompted us to focus on the role of p75NTR neurotrophin receptor (p75NTR) in dopaminergic neurodegeneration under hyperglycemic conditions.