Necroptosis in Down Syndrome

Necroptosis is a form of controlled cell death implicated in neuronal loss observed in neurodegenerative diseases such as Alzheimer's disease. Down syndrome (DS) is also characterized by the presence of neuronal cell loss, but the underlying mechanisms remain unclear. Brain tissue from a mouse model of DS, Ts65dn mice, and subjects with DS were assessed for levels of necroptosis markers including receptor-interactive protein kinase 1 and 3, necroptosis executor mixed lineage kinase domain-like protein and long non-coding RNA MEG. While no differences were observed between the Ts65dn and wild type mice at a young age, levels of these markers were significantly elevated in the brains of old DS mice when compared with matched wild type controls. Assessment of post-mortem brains from DS subjects also revealed a significant increase in these necroptosis markers. Our study is the first report showing the presence of necroptosis markers in the brains of a mouse model of DS and in DS subjects. These findings support the novel idea that this form of cell death should be also considered for developing novel therapeutic strategies for DS.