prostaglandin-d2 and Amyotrophic-Lateral-Sclerosis

Amyotrophic lateral sclerosis (ALS) is a late-onset, progressive motor neuronal degenerative disease occurring as sporadically and as a familial disorder. The patients with ALS typically become progressively paralyzed and develop respiratory failure that eventually leads to death within 3-5years. For this disease, there is no effective diagnostic method and also drug. This report describes a simple and useful diagnostic biomarker for ALS. Our findings suggest that the combination analysis of a metabolite of prostaglandin D2, 11,15-dioxo-9-hydroxy-,2,3,4,5-tetranorprostan-1,20-dioic acid (tetranor PGDM and tPGDM) with creatinine is the diagnostic approach for ALS with high accuracy. tPGDM has the potential to be an important diagnostic tool in the pre-symptomatic stages and progression evaluation of ALS, and also to be a biomarker for the evaluation of drug effect.

Topics: Aged; Amyotrophic Lateral Sclerosis; Biomarkers; Biomarkers, Pharmacological; Creatine; Humans; Male; Middle Aged; Prostaglandin D2; Urinalysis

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-enzymatically produced from PGD(2) 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.

Topics: Aged; Aged, 80 and over; Amyotrophic Lateral Sclerosis; Cell Line; Cyclopentanes; Cytoplasm; DNA-Binding Proteins; Female; Gene Expression Regulation; Humans; Immunologic Factors; Male; Middle Aged; Neuroblastoma; Prostaglandin D2; Spinal Cord; Subcellular Fractions