Lipocalin‐2 is increased in amyotrophic lateral sclerosis

Abstract

Introduction The exact mechanisms underlying neuroinflammation and how they contribute to amyotrophic lateral sclerosis (ALS) pathogenesis remain unclear. One possibility is the secretion of neurotoxic factors, such as lipocalin‐2 (LCN2), that lead to neuronal death. Methods LCN2 levels were measured in human post‐mortem tissue using western blot, qPCR, and immunofluorescence, and in plasma by ELISA. SH‐SY5Y cells were used to test the pro‐inflammatory effects of LCN2. Results LCN2 is increased in ALS post‐mortem motor cortex, spinal cord, and plasma. Furthermore, we identified several LCN2 variants in ALS patients that may contribute to disease pathogenesis. Lastly, while LCN2 treatment caused cell death and increased pro‐inflammatory markers, treatment with an anti‐LCN2 antibody prevented these responses in vitro. Discussion LCN2 upregulation in ALS post‐mortem samples and plasma may be an upstream event for triggering neuroinflammation and neuronal death.