＜Poster＞15-Deoxy-Δ^12,14-prostaglandin J_2 modifi es profi les of nuclear TDP-43 protein through its direct binding : Implication for the pathogenesis of TDP-43 proteinopathy

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  • 15 deoxy D 12 14 prostaglandin J2 modifies profiles of nuclear TDP 43 protein through its direct binding implication for the pathogenesis of TDP 43 proteinopathy

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TDP-43 proteinopathy （amyotrophic lateral sclerosis and frontotemporal lobar degeneration with ubiquitin-positive inclusions） is a newly categorized group of neurodegenerative disorders characterized by abnormal accumulation and mislocalization of nuclear TDP-43 protein in the neuronal cytoplasm. 15-deoxy-Δ12,14-prostaglandin J2 （15d-PGJ2） is non-enzymatically produced from PGD2, and plays roles in infl ammation and oxidative stress responses. Indeed, 15d-PGJ2 is up-regulated in the spinal motor neurons in ALS. In this study, biochemical and fluorescent staining analyses showed that 15d-PGJ2 modifi es expression, solubility, and subcellular localization of TDP-43. This alteration was at least partly related to a cyclopentenone ring structure containing an electrophilic carbon of 15d-PGJ2, because 15d-PGJ2 analogue, which lacks an cyclopentenone ring structure, had almost no eff ect on TDP-43 protein. Finally in vitro binding experiment indicated that 15d-PGJ2 is covalently bound to TDP-43 protein. These fi ndings suggest that a sustained high level of 15d-PGJ2 is involved in the pathogenesis of neurodegenerative disorders related to abnormal TDP-43 protein.

弘前医学. 61(Suppl.), 2010, p.S204-S210

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  • 弘前医学

    弘前医学 61 (Supplement), S204-S210, 2010-07-08

    弘前大学大学院医学研究科・弘前医学会

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