Association between oxidative stress and microRNA expression pattern of ALS patients in the high-incidence area of the Kii Peninsula.

Amyotrophic lateral sclerosis (ALS) is a progressive degenerative disorder of the upper and lower motor neuron systems. The high incidence of ALS in the southern part of the Kii Peninsula of Japan (K-ALS) was reported in the 1960s, but it has gradually decreased to the worldwide average. Although causes of the high incidence of ALS in this area are unknown, our previous studies suggested that environmental factors, including essential mineral deficiency and increased metal-induced oxidative stress, play a role in its development. Recently, it has been reported that microRNAs (miRNA) contribute to the degeneration of nervous system such as ALS. The aim of this study is to explore specific miRNAs in K-ALS and evaluate relationships between oxidative stress. We comprehensively analyzed serum miRNAs and examined urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), serum Cu/Zn superoxide dismutase (SOD) and serum Nɛ-hexanoyl lysin (HEL) as oxidative stress markers in the patients with K-ALS, sporadic ALS (S-ALS), residents in this area (K-residents) and controls from another area. The expression levels of miR-92a-3p and miR-486-5p in the patients with K-ALS were significantly higher than those in controls. The HEL levels were significantly higher in the patients with K-ALS than in those with S-ALS and controls. The expression levels of miR-92a-3p and miR-486-5p were not correlated with the levels of HEL. A set of high levels of miR-92a-3p, miR-486-5p and serum HEL may be a useful biomarker for K-ALS in the Kii Peninsula. The findings should be further studied by a large number of subjects.