中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (1): 113-114.doi: 10.4103/1673-5374.341042

• 观点:退行性病与再生 • 上一篇    下一篇

马铃薯白线虫，一种非转基因无脊椎动物，作为研究阿尔茨海默病（和其他蛋白质病）的新模型？

  

  • 出版日期:2023-01-15 发布日期:2022-06-16

Globodera pallida, a non-transgenic invertebrate as a new model for investigating Alzheimer’s disease (and other proteinopathies)?

Norah A. Althobaiti*, Farid Menaa*, Johnathan J. Dalzell,  Brian D. Green*    

  1. Biology Department, College of Science and Humanities-Al Quwaiiyah, Shaqra University, Al Quwaiiyah, Saudi Arabia (Althobaiti NA)
    Departments of Internal Medicine and Nanomedicine, Fluorotronics-California Innovations Corporation, San Diego, CA, USA (Menaa F)
    Department of grassland and Plant Science, AgriFood and Biosciences Institute, Northern Ireland, UK (Dalzell JJ)
    Institute for Global Food Security, School of Biological Sciences, Queen’s University Belfast, Belfast, UK (Green BD) 
  • Online:2023-01-15 Published:2022-06-16
  • Contact: Norah A. Althobaiti, PhD, nalthobaiti@su.edu.sa; Farid Menaa, MD, PhD, menaateam@gmail.com; Brian D. Green, PhD, b.green@qub.ac.uk.

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摘要： https://orcid.org/0000-0001-6893-5521 (Norah A. Althobaiti)
https://orcid.org/0000-0002-0258-7322 (Farid Menaa)
https://orcid.org/0000-0003-3331-0032 (Brian D. Green)


Abstract: Biological models of Alzheimer’s disease (AD): Non-human models have contributed tremendously to the understanding of AD and its underlying pathological processes. These models have aided the investigation of the genetic and environmental risk factors. They also have enabled the progression of candidate therapies into human clinical trials. Because of similarities with human brain anatomy and genetics, rodent models have been used extensively to recapitulate some aspects of AD pathology, measure AD-associated behavioral parameters and related nervous system dysfunctions (Eriksen and Janus, 2007). For instance, transgenic mice overexpressing human amyloid precursor protein have furthered the development of the amyloid cascade hypothesis as a central pillar of familial AD. Although considered as advantageous, mammalian models have practical and ethical problems when it comes to high-throughput screening (HTS) of drugs. Therefore, alternative models, including the use of invertebrates with very short lifecycles, represent rapid, simple, and highly cost-effective platforms for HTS or drug target identification (Artal‐Sanz et al., 2006). Indeed, the use of such organisms, as opposed to individual cell models, provides advantages for understanding the wider complexity of human pathology. Thereby, prominent invertebrate model organisms, such as Drosophila melanogaster (fruit fly), and the nematode Caenorhabditis elegans (roundworm), were insightful into the aging process, AD and Parkinson’s disease (Newman et al., 2011). The genome of D. melanogaster is ~70% homologous to that of humans and shows relatively complex brain and neuronal structures. Its eye is an accessible organ for phenotypic characterization, measuring of behavioral deficits, and determining responses to drug compounds. This fruit fly has unique learning and memory behaviors and can induce the gene expression of proteins considered to be the major hallmarks of AD, such as amyloid-beta (Aβ) or tau, both leading to AD pathological features and phenotypes. Furthermore, compounds such as GSK3-β inhibitors can rescue axonal transport and locomotion defects in these models. C. elegans is another invertebrate model organism employed in AD research. Several attempts have been made to use this free-living nematode (natively occurring in temperate soil environments) to generate transgenic AD models. One transgenic C. elegans model expressing Aβ peptides in muscle has a paralysis transgene-induced phenotype (Dostal and Link, 2010). Other models that neuronally express human Aβ exhibit phenotypes such as impaired chemotaxis and deficits in associated learning. Reported defects include impaired odor associative learning behavior, impaired serotonin-stimulated egg-laying, and decreased lifespan evidently resulting from Aβ toxicity.