Alteration of biochemical and pathological properties of TDP-43 protein by a lipid mediator, 15-deoxy-Delta(12,14)-prostaglandin J(2)

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-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) is non-enzyniatically produced from PGD2 and plays roles in Inflammation and oxidative stress responses Indeed, 15d-PGJ(2) is up-regulated in the spinal Motor neurons in amyotrophic lateral sclerosis In this Study, biochemical and immunocytochemical analyses showed that 15d-PGJ(2) affects the proteolysis, solubility, and subcellular localization of TDP-43. similar to alterations found in TDP-43 proteinopathy Further studies revealed that a cyclopentenone ring containing an electrophilic carbon of 15d-PGJ(2) is likely to influence these phenomena These findings suggest that 15d-PGJ(2) is an endogenous modifier of TDP-43 protein in TDP-43 proteinopathy (C) 2010 Elsevier Inc All rights reserved