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Biology subjects

U-on, N.

Publications and source records attributed to U-on, N..

2 recordsLinked to original sources

Diesel exhaust particles induce lasting and age-dependent damage to the brain in Drosophila melanogaster

Diesel exhaust particles (DEP), major air pollutants emitted from automobile engines, contain numerous toxic compounds. While the adverse effects of DEP exposure on the respiratory and cardiovascular systems are well documented, its impact on brain health remains poorly understood. In this study, we employed Drosophila melanogaster as a model organism to investigate the neurological effects of DEP exposure and the impact of exposure cessation across different age groups. Molecular, histopathological, and behavioral markers were assessed before and after exposure to varying doses of DEP at different time intervals.Interestingly, DEP exposure induced age-dependent cellular responses in the brain, including elevated reactive oxygen species (ROS), increased neuroinflammation, and disruption of the blood-brain barrier (BBB). Prolonged exposure led to pronounced vacuolization in the brains of aged flies. While cessation of DEP exposure resulted in partial recovery in young flies particularly when implemented early, aged flies exhibited limited benefit, with persistent evidence of likely irreversible brain damage. Overall, this study invites greater public awareness and careful consideration in public health policy to limit long-term DEP exposure, particularly among older individuals, and to encourage strategies that reduce potential risks to brain health associated with air pollution. Highlights1) DEP exposure is detrimental to the brain. 2) The brain responds to DEP exposure in an age-specific manner. 3) Permanent damage to the brain of old flies results from DEP exposure. 4) Cessation mitigates DEP-induced brain impairments when implemented at a young age. Environmental ImplicationOur study highlights the detrimental, age-dependent effects of diesel exhaust particle (DEP) exposure on brain health, underscoring the urgency of reducing air pollution. The findings support stricter environmental regulations to limit DEP emissions and promote cleaner transportation alternatives. Protecting vulnerable populations, particularly the elderly, from prolonged exposure may help mitigate the long-term neurological impacts of air pollutants and reduce the public health burden.

pharmacology and toxicology↗

Discovery of a pyrazolopyridine alkaloid inhibitor of ERO1A that mitigates neuronal ER stress and age-related decline

Endoplasmic reticulum (ER) stress contributes to the pathogenesis of neurodegenerative and age-associated diseases, motivating the search for compounds that enhance ER-stress resilience. Modulation of ER-redox pathways, including those associated with the oxidase ERO1A, can attenuate maladaptive unfolded protein response (UPR) signaling and improve cellular stress tolerance. Here we developed an integrative discovery strategy to identify natural compounds that mitigate ER-stress-associated phenotypes across cellular and organismal models. Structure-informed virtual screening guided by ERO1A biology prioritized the pyrazolopyridine alkaloid S88. In human SH-SY5Y-derived neurons, S88 improved survival and reduced tunicamycin-induced ER-stress markers. In Drosophila, S88 ameliorated neuromuscular and locomotor phenotypes in a UBQLN2-associated ALS model and improved aging-related outcomes. Biochemical assays did not detect inhibition of ERO1A or radical scavenging activity by S88, indicating that its molecular target remains to be identified. Together, these findings identify S88 as a natural-product scaffold that enhances ER-stress resilience across neuronal and in vivo models. Graphical abstract Structure-informed screening guided by ERO1A prioritized five natural products for functional validation across cellular and Drosophila models. The pyrazolopyridine alkaloid S88 consistently reduced ER-stress markers, improved neuronal survival, rescued locomotor and neuromuscular defects in an ALS model, and ameliorated aging phenotypes. The direct molecular target of S88 remains to be defined. Generated with assistance from the AI-based visualization tool NotebookLM and refined by the authors. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=185 SRC="FIGDIR/small/664722v2_ufig1.gif" ALT="Figure 1"> View larger version (104K): org.highwire.dtl.DTLVardef@8b97c0org.highwire.dtl.DTLVardef@97de54org.highwire.dtl.DTLVardef@857ce6org.highwire.dtl.DTLVardef@1cb1398_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗