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Lipocalin‐2 is increased in amyotrophic lateral sclerosis
Author(s) -
Petrozziello Tiziana,
Mills Alexandra N.,
Farhan Sali M.K.,
Mueller Kaly A.,
Granucci Eric J.,
Glajch Kelly E.,
Chan James,
Chew Sheena,
Berry James D.,
SadriVakili Ghazaleh
Publication year - 2020
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.26911
Subject(s) - neuroinflammation , amyotrophic lateral sclerosis , pathogenesis , western blot , lipocalin , downregulation and upregulation , neurodegeneration , medicine , biology , pathology , endocrinology , disease , biochemistry , gene
Background 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 postmortem tissue using Western blot, quantitative real time polymerase chain reaction, and immunofluorescence, and in plasma by enzyme‐linked immunosorbent assay. SH‐SY5Y cells were used to test the pro‐inflammatory effects of LCN2. Results LCN2 is increased in ALS postmortem 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 . Conclusions LCN2 upregulation in ALS postmortem samples and plasma may be an upstream event for triggering neuroinflammation and neuronal death.