Abstract
The social amoeba Dictyostelium discoideum is a model organism that is used to investigate many cellular processes including chemotaxis, cell motility, cell differentiation, and human disease pathogenesis. While many single-cellular model systems lack homologs of human disease genes, Dictyostelium’s genome encodes for many genes that are implicated in human diseases including neurodegenerative diseases. Due to its short doubling time along with the powerful genetic tools that enable rapid genetic screening, and the ease of creating knockout cell lines, Dictyostelium is an attractive model organism for both interrogating the normal function of genes implicated in neurodegeneration and for determining pathogenic mechanisms that cause disease. Here we review the literature involving the use of Dictyostelium to interrogate genes implicated in neurodegeneration and highlight key questions that can be addressed using Dictyostelium as a model organism.
Highlights
Reviewed by: Enrico Bracco, University of Turin, Italy Shuguang Yang, Institute of Basic Medical Sciences, China
Neurodegenerative disease progression inevitably leads to disability and death, and for most these diseases there is a lack of curative treatments
Hirano bodies were unable to form under Arp2/3 inhibition and in cells lacking vasodilator-stimulated phosphoprotein (VASP) or HSPC300, a protein involved in the WAVE (Wiskott-Aldrich Syndrome protein family verprolin-homologous protein) complex and activator of Arp2/3
Summary
Many non-mammalian model systems have numerous benefits including simpler genomes, decreased genetic redundancy, ease of genetic manipulation, shorter generation times, and scalability for high throughput genetic and pharmacological studies (van Ham et al, 2009; Gama Sosa et al, 2012; Bozarro, 2013; Suresh et al, 2018) These advantages allow for more rapid investigation into mechanisms that cause neurodegeneration that cannot be accomplished as in mammalian model systems. Dictyostelium consumes bacteria, when bacteria are depleted, Dictyostelium undergoes a developmental cycle transitioning from a unicellular amoeba to a multicellular fruiting body (Figure 1) This developmental process makes Dictyostelium an ideal model organism for investigating numerous biological processes including chemotaxis, cell differentiation, and tissue formation.
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