Dianxianning improved amyloid β-induced pathological characteristics partially through DAF-2/DAF-16 insulin like pathway in transgenic C. elegans

Zhi, Dejuan; Wang, Dong; Yang, Wenqi; Duan, Ziyun; Zhu, Shuqian; Dong, Juan; Wang, Na; Wang, Ningbo; Fei, Dong‐Qing; Zhang, Zhan‐Xin; Wang, Xin; Wang, Meizhu; Li, Hongyu

doi:10.1038/s41598-017-11628-9

Cited by 24 publications

(21 citation statements)

References 62 publications

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“…To determine whether CTS specifically reduces the levels of Aβ in muscle cells, this test was performed [ 60 ]. CL2179 was maintained and treated in the same way as the paralysis assay.…”

Section: Methodsmentioning

confidence: 99%

Cryptotanshinone Alleviates Oxidative Stress and Reduces the Level of Abnormally Aggregated Protein in Caenorhabditis elegans AD Models

Cui

Zhang

Bai

et al. 2022

IJMS

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Alzheimer’s disease (AD) is one of the leading causes of dementia. As the first common neurodegenerative disease, there are no effective drugs that can reverse the progression. The present study is to report the anti-AD effect of cryptotanshinone (CTS), a natural product isolated from Salvia castanea. It is found that it can alleviate AD-like features associated with Aβ1-42 toxicity in muscle cells as well as neuronal cells of Caenorhabditis elegans (C. elegans). Further studies showed that CTS reduced the level of reactive oxygen species (ROS) in nematodes, up-regulated the expression of sod-3, and enhanced superoxide dismutase activity. Cryptotanshinone reduced the level of Aβ monomers and highly toxic oligomers in C. elegans while inhibiting the abnormal aggregation of polyglutamine protein. In addition, CTS upregulated the expression of hsp-16.2 and downregulated the expression of ace-2. These results suggested that CTS could alleviate oxidative stress and reduce the level of abnormally aggregated proteins and has the potential to be developed as an anti-AD drug candidate.

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“…To determine whether CTS specifically reduces the levels of Aβ in muscle cells, this test was performed [ 60 ]. CL2179 was maintained and treated in the same way as the paralysis assay.…”

Section: Methodsmentioning

confidence: 99%

Cryptotanshinone Alleviates Oxidative Stress and Reduces the Level of Abnormally Aggregated Protein in Caenorhabditis elegans AD Models

Cui

Zhang

Bai

et al. 2022

IJMS

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“…More recently, Dianxianning, another traditional Chinese medicine, was found to reduce toxic Aβ species by a synergistic relationship between its ingredients. This activity was mediated through insulin signaling activated by oxidative stress responses, but independently from chaperone proteins and the Nrf orthologue, skn-1 . Similarly, phenolic extracts from maple syrup were found to reduce toxicity in human cell culture and C.…”

Section: Identifying Pharmacological Modifiers Of Aβ and Tau Toxicitymentioning

confidence: 97%

“…This activity was mediated through insulin signaling activated by oxidative stress responses, but independently from chaperone proteins and the Nrf orthologue, skn-1. 91 Similarly, phenolic extracts from maple syrup were found to reduce toxicity in human cell culture and C. elegans; though the contents of the extract had been characterized through HPLC-DAD, the way they coordinate to mediate protection from neurotoxicity of Aβ is unknown. 83 Drug screening techniques have been employed in multiple C. elegans models of neurodegenerative disease.…”

Section: ■ Discovering Genetic Modifiers Of Alzheimer's Diseasementioning

confidence: 99%

Genetic and Pharmacological Discovery for Alzheimer’s Disease Using Caenorhabditis elegans

Griffin

Caldwell

2017

ACS Chem. Neurosci.

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The societal burden presented by Alzheimer's disease warrants both innovative and expedient means by which its underlying molecular causes can be both identified and mechanistically exploited to discern novel therapeutic targets and strategies. The conserved characteristics, defined neuroanatomy, and advanced technological application of Caenorhabditis elegans render this metazoan an unmatched tool for probing neurotoxic factors. In addition, its short lifespan and importance in the field of aging make it an ideal organism for modeling age-related neurodegenerative disease. As such, this nematode system has demonstrated its value in predicting functional modifiers of human neurodegenerative disorders. Here, we review how C. elegans has been utilized to model Alzheimer's disease. Specifically, we present how the causative neurotoxic peptides, amyloid-β and tau, contribute to disease-like neurodegeneration in C. elegans and how they translate to human disease. Furthermore, we describe how a variety of transgenic animal strains, each with distinct utility, have been used to identify both genetic and pharmacological modifiers of toxicity in C. elegans. As technological advances improve the prospects for intervention, the rapidity, unparalleled accuracy, and scale that C. elegans offers researchers for defining functional modifiers of neurodegeneration should speed the discovery of improved therapies for Alzheimer's disease.

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“…The wild-type nematode N2 is sensitive to serotonin (5-HT), an important neurotransmitter that plays an important role in regulating nematode behaviors of olfactory learning, egg-laying, locomotion, and mating (Zhi et al, 2017). Exogenous 5-HT could inhibit C. elegans locomotion, leading active worms into paralysis.…”

Section: Oprr Alleviates Serotonin Hypersensitivity Caused By Aβ Expr...mentioning

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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Dianxianning improved amyloid β-induced pathological characteristics partially through DAF-2/DAF-16 insulin like pathway in transgenic C. elegans

Cited by 24 publications

References 62 publications

Cryptotanshinone Alleviates Oxidative Stress and Reduces the Level of Abnormally Aggregated Protein in Caenorhabditis elegans AD Models

Cryptotanshinone Alleviates Oxidative Stress and Reduces the Level of Abnormally Aggregated Protein in Caenorhabditis elegans AD Models

Genetic and Pharmacological Discovery for Alzheimer’s Disease Using Caenorhabditis elegans

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

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