Assessment and Validation of Globodera pallida as a Novel In Vivo Model for Studying Alzheimer’s Disease

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dc.contributor.authorAlthobaiti, Norah A.
dc.contributor.authorMenaa, Farid
dc.contributor.authorAlbalawi, Aishah E.
dc.contributor.authorDalzell, Johnathan
dc.contributor.authorWarnock, Neil
dc.contributor.authorMcCammick, Erin M.
dc.contributor.authorAlsolais, Abdulellah
dc.contributor.authorAlkhaibari, Abeer M.
dc.contributor.authorGreen, Brian D.
dc.date.accessioned2021-10-21T14:34:02Z
dc.date.available2021-10-21T14:34:02Z
dc.date.issued2021-09-19
dc.descriptionPublication history: Accepted - 11 September 2021; Published online - 19 September 2021.en_US
dc.description.abstractBackground: Whole transgenic or non-transgenic organism model systems allow the screening of pharmacological compounds for protective actions in Alzheimer’s disease (AD). Aim: In this study, a plant parasitic nematode, Globodera pallida, which assimilates intact peptides from the external environment, was investigated as a new potential non-transgenic model system of AD. Methods: Fresh second-stage juveniles of G. pallida were used to measure their chemosensory, perform immunocytochemistry on their neurological structures, evaluate their survival rate, measure reactive oxygen species, and determine total oxidized glutathione to reduced glutathione ratio (GSSG/GSH) levels, before and after treatment with 100 µM of various amyloid beta (Aβ) peptides (1–40, 1–42, 17–42, 17–40, 1–28, or 1–16). Wild-type N2 C. elegans (strain N2) was cultured on Nematode Growth Medium and directly used, as control, for chemosensory assays. Results: We demonstrated that: (i) G. pallida (unlike Caenorhabditis elegans) assimilates amyloid-β (Aβ) peptides which co-localise with its neurological structures; (ii) pre-treatment with various Aβ isoforms (1–40, 1–42, 17–42, 17–40, 1–28, or 1–16) impairs G. pallida’s chemotaxis to differing extents; (iii) Aβ peptides reduced survival, increased the production of ROS, and increased GSSG/GSH levels in this model; (iv) this unique model can distinguish differences between different treatment concentrations, durations, and modalities, displaying good sensitivity; (v) clinically approved neuroprotective agents were effective in protecting G. pallida from Aβ (1–42) exposure. Taken together, the data indicate that G. pallida is an interesting in vivo model with strong potential for discovery of novel bioactive compounds with anti-AD activity.en_US
dc.description.sponsorshipN.A.A. received a PhD studentship from Shaqra University, KSA and the Saudi Cultural Bureau in London (UKSACB). B.D.G.’s laboratory has received support for AD research from Alzheimer’s Research UK (ARUK-NC2019-NI), the Medical Research Council (MRC) (CIC-CD1718- CIC25), US-Ireland Health and Social Care NI (HSC R&DST/5460/2018) and InvestNI (RD101427 11-01-17-008). This work was also supported by Shaqra University, Saudi Arabiaen_US
dc.identifierhttp://hdl.handle.net/20.500.12518/365
dc.identifier.citationAlthobaiti, N. A., Menaa, F., Albalawi, A. E., Dalzell, J. J., Warnock, N. D., Mccammick, E. M., Alsolais, A., Alkhaibari, A. M. and Green, B. D. (2021) ‘Assessment and Validation of Globodera pallida as a Novel In Vivo Model for Studying Alzheimer’s Disease’, Cells. MDPI AG. doi: 10.3390/cells10092481.en_US
dc.identifier.issn2073-4409
dc.identifier.urihttps://doi.org/10.3390/cells10092481
dc.language.isoenen_US
dc.publisherMDPIen_US
dc.rightsCopyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).en_US
dc.subjectAlzheimer's diseaseen_US
dc.subjectamyloid-βen_US
dc.subjectGlobodera pallidaen_US
dc.subjectCaenorhabditis elegansen_US
dc.subjectoxidative stressen_US
dc.subjectin vivo modelen_US
dc.titleAssessment and Validation of Globodera pallida as a Novel In Vivo Model for Studying Alzheimer’s Diseaseen_US
dc.typeArticleen_US
dcterms.dateAccepted2021-09-11
dcterms.dateSubmitted2021-07-26

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