Queuine, a bacterial-derived hypermodified nucleobase, shows protection in in vitro models of neurodegeneration.

Growing evidence suggests that human gut bacteria, which comprise the microbiome, are linked to several neurodegenerative disorders. An imbalance in the bacterial population in the gut of Parkinson's disease (PD) and Alzheimer's disease (AD) patients has been detected in several studies. This dysbiosis very likely decreases or increases microbiome-derived molecules that are protective or detrimental, respectively, to the human body and those changes are communicated to the brain through the so-called 'gut-brain-axis'. The microbiome-derived molecule queuine is a hypermodified nucleobase enriched in the brain and is exclusively produced by bacteria and salvaged by humans through their gut epithelium. Queuine replaces guanine at the wobble position (position 34) of tRNAs with GUN anticodons and promotes efficient cytoplasmic and mitochondrial mRNA translation. Queuine depletion leads to protein misfolding and activation of the endoplasmic reticulum stress and unfolded protein response pathways in mice and human cells. Protein aggregation and mitochondrial impairment are often associated with neural dysfunction and neurodegeneration. To elucidate whether queuine could facilitate protein folding and prevent aggregation and mitochondrial defects that lead to proteinopathy, we tested the effect of chemically synthesized queuine, STL-101, in several in vitro models of neurodegeneration. After neurons were pretreated with STL-101 we observed a significant decrease in hyperphosphorylated alpha-synuclein, a marker of alpha-synuclein aggregation in a PD model of synucleinopathy, as well as a decrease in tau hyperphosphorylation in an acute and a chronic model of AD. Additionally, an associated increase in neuronal survival was found in cells pretreated with STL-101 in both AD models as well as in a neurotoxic model of PD. Measurement of queuine in the plasma of 180 neurologically healthy individuals suggests that healthy humans maintain protective levels of queuine. Our work has identified a new role for queuine in neuroprotection uncovering a therapeutic potential for STL-101 in neurological disorders.

Cometabolic biodegradation of methyl tert-butyl ether by a soil consortium: Effect of components present in gasoline.

A soil consortium was tested for its ability to degrade reformulated gasoline, containing methyl tert-butyl ether (MTBE). Reformulated gasoline was rapidly degraded to completion. However, MTBE tested alone was not degraded. A screening was carried out to identify compounds in gasoline that participate in cometabolism with MTBE. Aromatic compounds (benzene, toluene, xylenes) and compounds structurally similar to MTBE (tert-butanol, 2,2-dimethylbutane, 2,2,4-trimethylpentane) were unable to cometabolize MTBE. Cyclohexane was resistant to degradation. However, all n-alkanes tested for cometabolic activity (pentane, hexane, heptane) did enable the biodegradation of MTBE. Among the alkanes tested, pentane was the most efficient (200 &mgr;g/day). Upon the depletion of pentane, the consortium stopped degrading MTBE. When the consortium was spiked with pentane, MTBE degradation continued. When the ratio of MTBE to pentane was increased, the amount of MTBE degraded by the consortium was higher. Finally, diethylether was tested for cometabolic degradation with MTBE. Both compounds were degraded, but the process differed from that observed with pentane.