Lactate dehydrogenase expression modulates longevity and neurodegeneration in Drosophila melanogaster
| العنوان: | Lactate dehydrogenase expression modulates longevity and neurodegeneration in Drosophila melanogaster |
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| المؤلفون: | David A. Hendrix, Robert C. Cumming, Patrick N. Reardon, Dani M Long, Ariel K. Frame, Jadwiga M. Giebultowicz, Doris Kretzschmar |
| المصدر: | Aging (Albany NY) Paediatrics Publications |
| بيانات النشر: | Impact Journals, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Male, medicine.medical_specialty, Cell type, Aging, media_common.quotation_subject, Longevity, Animals, Genetically Modified, chemistry.chemical_compound, Internal medicine, Lactate dehydrogenase, Gene expression, medicine, Animals, Drosophila Proteins, Humans, Circadian rhythms, Circadian rhythm, Lactic Acid, Neurodegeneration, media_common, Neurons, lactate, biology, L-Lactate Dehydrogenase, Chemistry, aging, neurodegeneration, Brain, lactate dehydrogenase, Cell Biology, medicine.disease, biology.organism_classification, Enzyme assay, Circadian Rhythm, Endocrinology, Drosophila melanogaster, circadian rhythms, biology.protein, Female, lifespan, Locomotion, Priority Research Paper |
| الوصف: | Lactate dehydrogenase (LDH) catalyzes the conversion of glycolysis-derived pyruvate to lactate. Lactate has been shown to play key roles in brain energetics and memory formation. However, lactate levels are elevated in aging and Alzheimer's disease patients, and it is not clear whether lactate plays protective or detrimental roles in these contexts. Here we show that Ldh transcript levels are elevated and cycle with diurnal rhythm in the heads of aged flies and this is associated with increased LDH protein, enzyme activity, and lactate concentrations. To understand the biological significance of increased Ldh gene expression, we genetically manipulated Ldh levels in adult neurons or glia. Overexpression of Ldh in both cell types caused a significant reduction in lifespan whereas Ldh down-regulation resulted in lifespan extension. Moreover, pan-neuronal overexpression of Ldh disrupted circadian locomotor activity rhythms and significantly increased brain neurodegeneration. In contrast, reduction of Ldh in neurons delayed age-dependent neurodegeneration. Thus, our unbiased genetic approach identified Ldh and lactate as potential modulators of aging and longevity in flies. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1945-4589 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::873fb6b30eb026a9097ae185b5e6bcd7 http://europepmc.org/articles/PMC7346061 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....873fb6b30eb026a9097ae185b5e6bcd7 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19454589 |
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