The association of α-amino-β-methylaminopropionic acid (BMAA) with elevated incidence of amyotrophic lateral sclerosis/Parkinson’s disease complex (ALS/PDC) was first identified on the island of Guam. BMAA has been shown to be produced across the cyanobacterial order and its detection has been reported in a variety of aquatic and terrestrial environments worldwide, suggesting that it is ubiquitous. Various in vivo studies on rats, mice, chicks and monkeys have shown that it can cause neurodegenerative symptoms such as ataxia and convulsions. Zebrafish research has also shown disruption to neural development after BMAA exposure. In vitro studies on mice, rats and leeches have shown that BMAA acts predominantly on motor neurons. Observed increases in the generation of reactive oxygen species (ROS) and Ca2+ influx, coupled with disruption to mitochondrial activity and general neuronal death, indicate that the main mode of activity is via excitotoxic mechanisms. The current review pertaining to the neurotoxicity of BMAA clearly demonstrates its ability to adversely affect neural tissues, and implicates it as a potentially significant compound in the aetiology of neurodegenerative disease. When considering the potential adverse health effects upon exposure to this compound, further research to better understand the modes of toxicity of BMAA and the environmental exposure limits is essential.
Glutathione (GSH) is one of the most abundant thiol antioxidants in cells. Many chronic and age-related diseases are associated with a decline in cellular GSH levels or impairment in the catalytic activity of the GSH biosynthetic enzyme glutamate cysteine ligase (GCL). γ-glutamylcysteine (GGC), a precursor to glutathione (GSH), can replenish depleted GSH levels under oxidative stress conditions, by circumventing the regulation of GSH biosynthesis and providing the limiting substrate. Soluble amyloid-β (Aβ) oligomers have been shown to induce oxidative stress, synaptic dysfunction and memory deficits which have been reported in Alzheimer’s disease (AD). Calcium ions, which are increased with age and in AD, have been previously reported to enhance the formation of Aβ 40 oligomers, which have been casually associated with the pathogenesis of the underlying neurodegenerative condition. In this study, we examined the potential beneficial effects of GGC against exogenous Aβ 40 oligomers on biomarkers of apoptosis and cell death, oxidative stress, and neuroinflammation, in human astrocytes. Treatment with Aβ 40 oligomers significantly reduced the cell viability and apoptosis of astrocyte brain cultures and increased oxidative modifications of DNA, lipids, and protein, enhanced pro-inflammatory cytokine release and increased the activity of the proteolytic matrix metalloproteinase enzyme, matric metalloproteinase (MMP)-2 and reduced the activity of MMP-9 after 24 h. Co-treatment of Aβ 40 oligomers with GGC at 200 μM increased the activity of the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx) and led to significant increases in the levels of the total antioxidant capacity (TAC) and GSH and reduced the GSSG/GSH ratio. GGC also upregulated the level of the anti-inflammatory cytokine IL-10 and reduced the levels of the pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) and attenuated the changes in metalloproteinase activity in oligomeric Aβ 40 -treated astrocytes. Our data provides renewed insight on the beneficial effects of increased GSH levels by GGC in human astrocytes, and identifies yet another potential therapeutic strategy to attenuate the cytotoxic effects of Aβ oligomers in AD.
Background: Cell adhesion molecule CHL1 plays a dual role by either promoting or inhibiting neuritogenesis. Results: Ligand-induced clustering of CHL1 at the cell surface induces lipid raft-dependent endocytosis of CHL1 and neuritogenesis. Conclusion: Ligand-induced remodeling of CHL1 adhesion promotes neurite outgrowth. Significance: High levels of CHL1 adhesion and inhibition of CHL1 endocytosis can interfere with neuronal development and/or regeneration.
Hydrogenases are found in a wide range of archaea, prokaryotes and eukaryotes as soluble and membrane-bound enzymes and are generally classified by the structure of the catalytic site. From a biotechnological perspective, hydrogenases have been examined for their role in the production of biohydrogen; for co-factor regeneration in coupled enzyme reactions; for environmental applications, and for the electrochemical oxidation of molecular hydrogen. Hydrogenases, with their ability to readily oxidise hydrogen or reduce protons into hydrogen, have huge potential as biocatalysts in many emerging technologies based on the use of hydrogen as a clean energy vector. This review will focus on the hydrogenases associated with the oxidation of molecular hydrogen (so-called ''uptake hydrogenases'' (EC 1.12.99.6)), covering their properties, structure, isolation, and remaining barriers for potential industrial applications, including bio-fuel cells, photocatalytic water splitting and hydrogen sensors.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.