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Review
. 2024 Mar 4:17:1328578.
doi: 10.3389/fnmol.2024.1328578. eCollection 2024.

Invertebrate genetic models of amyotrophic lateral sclerosis

LiJun Zhou  1   2 , RenShi Xu  1   2
Affiliations
Review

Invertebrate genetic models of amyotrophic lateral sclerosis

LiJun Zhou et al. Front Mol Neurosci. .

Abstract

Amyotrophic lateral sclerosis (ALS) is a common adult-onset neurodegenerative disease characterized by the progressive death of motor neurons in the cerebral cortex, brain stem, and spinal cord. The exact mechanisms underlying the pathogenesis of ALS remain unclear. The current consensus regarding the pathogenesis of ALS suggests that the interaction between genetic susceptibility and harmful environmental factors is a promising cause of ALS onset. The investigation of putative harmful environmental factors has been the subject of several ongoing studies, but the use of transgenic animal models to study ALS has provided valuable information on the onset of ALS. Here, we review the current common invertebrate genetic models used to study the pathology, pathophysiology, and pathogenesis of ALS. The considerations of the usage, advantages, disadvantages, costs, and availability of each invertebrate model will also be discussed.

Keywords: Caenorhabditis elegans; Drosophila melanogaster; FUS; SOD1; TDP-43; amyotrophic lateral sclerosis; invertebrate models; yeast.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
The commonly used invertebrate genetic models of ALS. The highly manipulative genomes of these models allow us to rapidly reproduce the transgenic lines for providing the ideal models for studying the gene functions and protein network interactions. The finds from the established models identified some key genes to involve in cell division, differentiation and apoptosis, which structures and functions were the high conservation with higher animals including humans, and it is easy access to the full sequence of model genomes. The model organisms have more significant experimental advantages, such as the short generate time, small sizes, easy maintenance as well as less cost. Besides, it is amenable to the genetic approaches of both forward and reverse. However, these invertebrate animal models are evolutionarily far from higher animal and mammalians, therefore, lots of physiologic functions can't be observed. The organs are extremely undeveloped as well as the limited cellular diversity, so it isn't beneficial to study the pathological alteration of organs and cellular levels. ALS, amyotrophic lateral sclerosis.
Figure 2
Figure 2
The features and applications of Yeasts genetic models in ALS. ALS, amyotrophic lateral sclerosis; EWS, Ewing sarcoma breakpoint region 1; FUS, fused in sarcoma; hnRNPA2, heterogeneous nuclear ribonucleoprotein A2; TAF15, TATA-box binding protein associated factor 15; TDP-43, TAR DNA-binding protein 43.
Figure 3
Figure 3
The features and applications of D. melanogaster genetic models in ALS. ALS, amyotrophic lateral sclerosis; D. melanogaster, Drosophila melanogaster.
Figure 4
Figure 4
The features and applications of C. elegans genetic models in ALS. ALS, amyotrophic lateral sclerosis; C. elegans, Caenorhabditis elegans; γ-GABA, gamma-aminobutyric acid.
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References

    1. Alberti A., Michelet X., Djeddi A., Legouis R. (2010). The autophagosomal protein LGG-2 acts synergistically with LGG-1 in dauer formation and longevity in C. elegans. Autophagy 6, 622–633. 10.4161/auto.6.5.12252 - DOI - PubMed
    1. An L., Harrison P. M. (2016). The evolutionary scope and neurological disease linkage of yeast-prion-like proteins in humans. Biol. Direct 11, 32. 10.1186/s13062-016-0134-5 - DOI - PMC - PubMed
    1. Ash P. E. A., Zhang Y.-J., Roberts C. M., Saldi T., Hutter H., Buratti E., et al. . (2010). Neurotoxic effects of TDP-43 overexpression in C. elegans. Hum. Mol. Genet. 19, 3206–3218. 10.1093/hmg/ddq230 - DOI - PMC - PubMed
    1. Azoulay-Ginsburg S., Di Salvio M., Weitman M., Afri M., Ribeiro S., Ebbinghaus S., et al. . (2021). Chemical chaperones targeted to the endoplasmic reticulum (ER) and lysosome prevented neurodegeneration in a C9orf72 repeat expansion Drosophila amyotrophic lateral sclerosis (ALS) model. Pharmacol. Rep. 73, 536–550. 10.1007/s43440-021-00226-2 - DOI - PubMed
    1. Azuma Y., Mizuta I., Tokuda T., Mizuno T. (2018). Amyotrophic lateral sclerosis model. Adv. Exp. Med. Biol. 1076, 79–95. 10.1007/978-981-13-0529-0_6 - DOI - PubMed

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. Open access funding was provided by the Committee of the National Natural Science Foundation of China (82160255), Jiangxi Provincial Department of Science and Technology (20192BAB205043), and the Health and Family Planning Commission of Jiangxi Province (202210002 and 202310119).

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