Exploring the conservation of Alzheimer-related pathways between H. sapiens and C. elegans: a network alignment approach

Apostolakou, Avgi E; Sula, Xhuliana K; Nastou, Katerina C.; Nasi, Georgia I.; Iconomidou, Vassiliki A.

doi:10.1038/s41598-021-83892-9

Cited by 14 publications

(9 citation statements)

References 64 publications

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“…Interaction networks were assembled for the APP and tau proteins in H. sapiens , and their orthologues APL-1 and PTL-1 in C. elegans . Using Global Network Alignment for comparison, it was found that both APP processing and tau phosphorylation pathways are highly conserved in both organisms [ 24 ]. Therefore, the interaction pathways of these AD-related proteins are closely matched.…”

Section: The C Elegans Model: Advantages and Limit...mentioning

confidence: 99%

Modeling Alzheimer’s Disease in Caenorhabditis elegans

et al. 2022

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Alzheimer’s disease (AD) is the most frequent cause of dementia. After decades of research, we know the importance of the accumulation of protein aggregates such as β-amyloid peptide and phosphorylated tau. We also know that mutations in certain proteins generate early-onset Alzheimer’s disease (EOAD), and many other genes modulate the disease in its sporadic form. However, the precise molecular mechanisms underlying AD pathology are still unclear. Because of ethical limitations, we need to use animal models to investigate these processes. The nematode Caenorhabditis elegans has received considerable attention in the last 25 years, since the first AD models overexpressing Aβ peptide were described. We review here the main results obtained using this model to study AD. We include works studying the basic molecular mechanisms of the disease, as well as those searching for new therapeutic targets. Although this model also has important limitations, the ability of this nematode to generate knock-out or overexpression models of any gene, single or combined, and to carry out toxicity, recovery or survival studies in short timeframes with many individuals and at low cost is difficult to overcome. We can predict that its use as a model for various diseases will certainly continue to increase.

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Section: The C Elegans Model: Advantages and Limit...mentioning

confidence: 99%

Modeling Alzheimer’s Disease in Caenorhabditis elegans

et al. 2022

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“…All these advantages make this nematode an ideal living system for AD studies. In addition, both tau phosphorylation and APP processing pathway are highly conserved in Homo sapiens and C. elegans (Apostolakou et al, 2021). Although C. elegans cannot generate endogenous Aβ because of the absence of β-secretase, exogenous expression methods have remedied this limitation by producing human β-amyloid peptides in muscle cells and pan neurons (Griffin et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective Effects of Oligosaccharides in Rehmanniae Radix on Transgenic Caenorhabditis elegans Models for Alzheimer’s Disease

et al. 2022

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Rehmanniae Radix (RR, the dried tuberous roots of Rehmannia glutinosa (Gaertn.) DC.) is an important traditional Chinese medicine distributed in Henan, Hebei, Inner Mongolia, and Northeast in China. RR is frequently used to treat diabetes mellitus, cardiovascular disease, osteoporosis and aging-related diseases in a class of prescriptions. The oligosaccharides and catalpol in RR have been confirmed to have neuroprotective effects. However, there are few studies on the anti-Alzheimer’s disease (AD) effect of oligosaccharides in Rehmanniae Radix (ORR). The chemical components and pharmacological effects of dried Rehmannia Radix (DRR) and prepared Rehmannia Radix (PRR) are different because of the different processing methods. ORR has neuroprotective potential, such as improving learning and memory in rats. Therefore, this study aimed to prove the importance of oligosaccharides in DRR (ODRR) and PRR (OPRR) for AD based on the Caenorhabditis elegans (C. elegans) model and the different roles of ODRR and OPRR in the treatment of AD. In this study, we used paralysis assays, lifespan and stress resistance assays, bacterial growth curve, developmental and behavioral parameters, and ability of learning and memory to explore the effects of ODRR and OPRR on anti-AD and anti-aging. Furthermore, the accumulation of reactive oxygen species (ROS); deposition of Aβ; and expression of amy-1, sir-2.1, daf-16, sod-3, skn-1, and hsp-16.2 were analyzed to confirm the efficacy of ODRR and OPRR. OPRR was more effective than ODRR in delaying the paralysis, improving learning ability, and prolonging the lifespan of C. elegans. Further mechanism studies showed that the accumulation of ROS, aggregation, and toxicity of Aβ were reduced, suggesting that ORR alleviated Aβ-induced toxicity, in part, through antioxidant activity and Aβ aggregation inhibiting. The expression of amy-1 was downregulated, and sir-2.1, daf-16, sod-3, and hsp-16.2 were upregulated. Thus, ORR could have a possible therapeutic effect on AD by modulating the expression of amy-1, sir-2.1, daf-16, sod-3, and hsp-16.2. Furthermore, ORR promoted the nuclear localization of daf-16 and further increased the expression of sod-3 and hsp-16.2, which significantly contributed to inhibiting the Aβ toxicity and enhancing oxidative stress resistance. In summary, the study provided a new idea for the development of ORR.

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“…Many studies have demonstrated the usefulness of C. elegans as a tool to study the underlying mechanisms that give rise to aging-associated neurodegenerative diseases, including Alzheimer’s disease [ 139 , 140 ], and other age-related conditions like sarcopenia, because this nematode also shows loss of muscle mass with aging [ 141 ]. Moreover, C. elegans not only allows effects in behavioural and molecular improvements to be determined, but also modulation of lifespan caused by the studied substance [ 142 ].…”

Section: High-throughput Techniques and Biological Models To Study Om...mentioning

confidence: 99%

Structured Long-Chain Omega-3 Fatty Acids for Improvement of Cognitive Function during Aging

Mora

Arola

Caimari

et al. 2022

IJMS

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Although the human lifespan has increased in the past century owing to advances in medicine and lifestyle, the human healthspan has not kept up the same pace, especially in brain aging. Consequently, the role of preventive health interventions has become a crucial strategy, in particular, the identification of nutritional compounds that could alleviate the deleterious effects of aging. Among nutrients to cope with aging in special cognitive decline, the long-chain omega-3 polyunsaturated fatty acids (ω-3 LCPUFAs) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), have emerged as very promising ones. Due to their neuroinflammatory resolving effects, an increased status of DHA and EPA in the elderly has been linked to better cognitive function and a lower risk of dementia. However, the results from clinical studies do not show consistent evidence and intake recommendations for old adults are lacking. Recently, supplementation with structured forms of EPA and DHA, which can be derived natural forms or targeted structures, have proven enhanced bioavailability and powerful benefits. This review summarizes present and future perspectives of new structures of ω-3 LCPUFAs and the role of “omic” technologies combined with the use of high-throughput in vivo models to shed light on the relationships and underlying mechanisms between ω-3 LCPUFAs and healthy aging.

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Exploring the conservation of Alzheimer-related pathways between H. sapiens and C. elegans: a network alignment approach

Cited by 14 publications

References 64 publications

Modeling Alzheimer’s Disease in Caenorhabditis elegans

Modeling Alzheimer’s Disease in Caenorhabditis elegans

Neuroprotective Effects of Oligosaccharides in Rehmanniae Radix on Transgenic Caenorhabditis elegans Models for Alzheimer’s Disease

Structured Long-Chain Omega-3 Fatty Acids for Improvement of Cognitive Function during Aging

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