Mutations in human Cu,Zn-superoxide dismutase (SOD1) cause approximately 20% of familial amyotrophic lateral sclerosis (FALS) cases. The mechanism of late-onset disease manifestation despite the innate mutation has no clear explanation. The relationship between homocysteine (HC) and amyotrophic lateral sclerosis (ALS) has not been investigated, in spite of the similarity in their pathogenesis. We investigated the effect of HC on the motor neuronal cell-line transfected with SOD1 of either wild-type or one of two mutant forms (G93A and A4V). In the MTT assay, HC induced significant cytotoxicity in A4V, but not in G93A, as compared with wild-type, even at the physiological concentration of 10 microM. This HC-induced cytotoxicity was inhibited by the antioxidant trolox and the Cu (I) chelator bathocuproinedisulfonate. Here we show that the vulnerability of the A4 V mutant involves the cytotoxic copper-mediated pathway, and that HC may be a lifelong precipitating factor in some forms of FALS, suggesting the possible treatment modality with vitamin supplements.

In this study, the immunoactive effect of Gryllus bimaculatus water extract (GBWE) on macrophages was investigated under various extraction temperature conditions. The study found that GBWE did not induce cytotoxicity in RAW 264.7 cells within the tested concentration range. Treatment with GBWE under different extraction conditions resulted in an increase in cytokine secretion and nitric oxide production in the treated cells. Furthermore, the treatment with GBWE increased the expression of surface molecules, and GBWE-treated cells showed phosphorylation of mitogen-activated protein kinases and nuclear factor-kappa B translocation. The experimental results suggest that GBWE exhibits immune-enhancing effects in macrophages. Notably, these effects were observed even in GBWE extracted at low temperatures (5℃ and 25℃) without exposure to high temperatures (75℃) typically used for extraction. These findings suggest that GBWE has the potential to be used as an alternative protein source and functional food material with immunostimulatory properties.

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