Disrupted expression of mitochondrial NCLX sensitizes neuroglial networks to excitotoxic stimuli and renders synaptic activity toxic
Anna M. Hagenston, Jing Yan, Carlos Bas‐Orth, Yan-Wei Tan, Israel Sekler, Hilmar Bading
Abstract
breakdown and substantial neurodegeneration in hippocampal cultures undergoing synaptic activity. Finally, we showed that NCLX knockdown within the hippocampal cornu ammonis 1 region in vivo causes substantial neurodegeneration and astrodegeneration. In summary, we demonstrated that dysregulated NCLX expression not only sensitizes neuroglial networks to excitotoxic stimuli but also notably renders otherwise neuroprotective synaptic activity toxic. These findings may explain the emergence of neurodegeneration and astrodegeneration in patients with disorders characterized by disrupted NCLX expression or function, and suggest that treatments aimed at enhancing or restoring NCLX function may prevent central nervous system damage in these disease states.