Somatic expression of unc-54 and vha-6 mRNAs declines but not pan-neuronal rgef-1 and unc-119 expression in aging Caenorhabditis elegans

Adamla, Frauke; Ignatova, Zoya

doi:10.1038/srep10692

Cited by 12 publications

(13 citation statements)

References 54 publications

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“…Even more pronounced effects were monitored by using HT, with a reduction of α-synuclein accumulation by 6% at day 3, 7% at day 7, and 14% at day 12 of adulthood. Overall, the fluorescence intensity declined with age, a finding in line with the ageing-dependent decline of unc-54 expression observed by Adamla and Ignatova [66].…”

Section: α-Synuclein Induced Damages and α-Synuclein Accumulation Wassupporting

confidence: 86%

Healthspan Maintenance and Prevention of Parkinson’s-like Phenotypes with Hydroxytyrosol and Oleuropein Aglycone in C. elegans

Brunetti

Rosa

Scuto

et al. 2020

IJMS

123

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Numerous studies highlighted the beneficial effects of the Mediterranean diet (MD) in maintaining health, especially during ageing. Even neurodegeneration, which is part of the natural ageing process, as well as the foundation of ageing-related neurodegenerative disorders like Alzheimer’s and Parkinson’s disease (PD), was successfully targeted by MD. In this regard, olive oil and its polyphenolic constituents have received increasing attention in the last years. Thus, this study focuses on two main olive oil polyphenols, hydroxytyrosol (HT) and oleuropein aglycone (OLE), and their effects on ageing symptoms with special attention to PD. In order to avoid long-lasting, expensive, and ethically controversial experiments, the established invertebrate model organism Caenorhabditis elegans was used to test HT and OLE treatments. Interestingly, both polyphenols were able to increase the survival after heat stress, but only HT could prolong the lifespan in unstressed conditions. Furthermore, in aged worms, HT and OLE caused improvements of locomotive behavior and the attenuation of autofluorescence as a marker for ageing. In addition, by using three different C. elegans PD models, HT and OLE were shown i) to enhance locomotion in worms suffering from α-synuclein-expression in muscles or rotenone exposure, ii) to reduce α-synuclein accumulation in muscles cells, and iii) to prevent neurodegeneration in α-synuclein-containing dopaminergic neurons. Hormesis, antioxidative capacities and an activity-boost of the proteasome & phase II detoxifying enzymes are discussed as potential underlying causes for these beneficial effects. Further biological and medical trials are indicated to assess the full potential of HT and OLE and to uncover their mode of action.

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Section: α-Synuclein Induced Damages and α-Synuclein Accumulation Wassupporting

confidence: 86%

Healthspan Maintenance and Prevention of Parkinson’s-like Phenotypes with Hydroxytyrosol and Oleuropein Aglycone in C. elegans

Brunetti

Rosa

Scuto

et al. 2020

IJMS

123

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“…Difference in abundance of RP mRNAs across tissues (11) cannot be extrapolated to their protein levels, since posttranscriptional processing actively buffers protein concentration (5). Protein dynamics is shaped by mRNA and protein half-lives, both of which differ among individual transcripts and proteins but also exhibit a tissue-specific pattern of stability with somewhat higher stability in neuronal tissues (8)(9)(10)(11). A recent study in a genetically well-tractable system, C. elegans (28), and earlier observations in Xenopus embryos (45) suggests that tissue diversification may not rely on ribosomes with a heterogeneous RP pool.…”

Section: Discussionmentioning

confidence: 99%

“…Various tissues also exhibit different transcript dynamics over age. In brain tissues of Caenorhabditis elegans or the short-lived fish Nothobranchius fuzeri, the RP mRNA levels increase with age, while in other tissues they decrease or remain constant (9)(10)(11). In addition, individual RPs are exchanged at different rates with the cytoplasmic pool of their free counterparts (12,13).…”

Section: Invariable Stoichiometry Of Ribosomal Proteins In Mouse Braimentioning

confidence: 99%

Invariable stoichiometry of ribosomal proteins in mouse brain tissues with aging

Amirbeigiarab

Kiani

Sanchez

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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Across phyla, the ribosomes—the central molecular machines for translation of genetic information—exhibit an overall preserved architecture and a conserved functional core. The natural heterogeneity of the ribosome periodically phases a debate on their functional specialization and the tissue-specific variations of the ribosomal protein (RP) pool. Using sensitive differential proteomics, we performed a thorough quantitative inventory of the protein composition of ribosomes from 3 different mouse brain tissues, i.e., hippocampus, cortex, and cerebellum, across various ages, i.e., juvenile, adult, and middle-aged mouse groups. In all 3 brain tissues, in both monosomal and polysomal ribosome fractions, we detected an invariant set of 72 of 79 core RPs, RACK1 and 2 of the 8 RP paralogs, the stoichiometry of which remained constant across different ages. The amount of a few RPs punctually varied in either one tissue or one age group, but these fluctuations were within the tight bounds of the measurement noise. Further comparison with the ribosomes from a high-metabolic-rate organ, e.g., the liver, revealed protein composition identical to that of the ribosomes from the 3 brain tissues. Together, our data show an invariant protein composition of ribosomes from 4 tissues across different ages of mice and support the idea that functional heterogeneity may arise from factors other than simply ribosomal protein stoichiometry.

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“…Consistent with the observed defects in nociceptive sensing, extracellular V30M TTR resulted in defective FLP dendritic branch extension and in ectopic branching that appeared to be due to degenerative processes rather than developmental defects. As nociceptive sensing was only partially impaired in V30M TTR animals, it is possible that TTR proteotoxicity primarily impaired FLP function, whereas AFD, the other neurons responsible for nociception (30,32), were less affected; however, this needs to be evaluated further. Putative sensory neuron selectivity would suggest a specific TTR-targeting mechanism.…”

Section: A Model To Study Cell-nonautonomous Proteostatic Mechanisms Formentioning

confidence: 98%

Cellular clearance of circulating transthyretin decreases cell-nonautonomous proteotoxicity in Caenorhabditis elegans

Madhivanan

Greiner

Alves‐Ferreira

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

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Cell-autonomous and cell-nonautonomous mechanisms of neurodegeneration appear to occur in the proteinopathies, including Alzheimer's and Parkinson's diseases. However, how neuronal toxicity is generated from misfolding-prone proteins secreted by nonneuronal tissues and whether modulating protein aggregate levels at distal locales affects the degeneration of postmitotic neurons remains unknown. We generated and characterized animal models of the transthyretin (TTR) amyloidoses that faithfully recapitulate cell-nonautonomous neuronal proteotoxicity by expressing human TTR in the muscle. We identified sensory neurons with affected morphological and behavioral nociception-sensing impairments. Nonnative TTR oligomer load and neurotoxicity increased following inhibition of TTR degradation in distal macrophage-like nonaffected cells. Moreover, reducing TTR levels by RNAi or by kinetically stabilizing natively folded TTR pharmacologically decreased TTR aggregate load and attenuated neuronal dysfunction. These findings reveal a critical role for modulation of aggregation-prone degradation that directly affects postmitotic tissue degeneration observed in the proteinopathies.

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Somatic expression of unc-54 and vha-6 mRNAs declines but not pan-neuronal rgef-1 and unc-119 expression in aging Caenorhabditis elegans

Cited by 12 publications

References 54 publications

Healthspan Maintenance and Prevention of Parkinson’s-like Phenotypes with Hydroxytyrosol and Oleuropein Aglycone in C. elegans

Healthspan Maintenance and Prevention of Parkinson’s-like Phenotypes with Hydroxytyrosol and Oleuropein Aglycone in C. elegans

Invariable stoichiometry of ribosomal proteins in mouse brain tissues with aging

Cellular clearance of circulating transthyretin decreases cell-nonautonomous proteotoxicity in Caenorhabditis elegans

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