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Inositol Hexakisphosphate Kinase 2 is a Presymptomatic Biomarker for Amyotrophic Lateral Sclerosis
Yusuke Moriya1, Eiichiro Nagata, Natsuko Fujii
1Department of Neurology, Tokai University school of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan. moriya-y@is.icc.u-tokai.ac.jp.
Objective:
Inositol hexakisphosphate kinase 2 (InsP6K2), an enzyme that converts inositol hexakisphosphate (InsP6) to diphosphoinositol pentakisphosphate (InsP7), induces cell death. InsP6K2 is abundant in the central nervous system, especially anterior horn cells of spinal cord. To identify the role of InsP6K2 in amyotrophic lateral sclerosis (ALS), we investigated the expression levels of InsP6K2 in transgenic mice expressing mutant superoxide dismutase-1 (SOD1) (mSOD1 Tg mice).
Methods:
The specimens of spinal cords were obtained from mSOD1 Tg mice and age-matched wild-type mice. We investigated the expression of InsP6K2 at the gene and protein levels of the spinal cord in mSOD1 Tg and wild-type mice.
Results:
The gene expression levels of InsP6K2 in mSOD1 Tg mice was significantly higher than that in wild-type mice before ALS symptoms developed. In immunohistochemistry and western blotting results showed that InsP6K2 translocated from the nucleus to the cytoplasm in mSOD1 Tg mice.
Conclusion:
These findings suggest that InsP6K2 activates in mSOD1 Tg mice before the onset of ALS. Therefore, InsP6K2 might be a presymptomatic biomarker for ALS.