Identification of compounds and genes that affect neurodegenerative diseases in Caenorhabditis elegans

  1. N. Bellido-Alocolea
  2. M. M. Pérez-Jiménez
  3. M. J. Muñoz
Biosaia: Revista de los másteres de Biotecnología Sanitaria y Biotecnología Ambiental, Industrial y Alimentaria

ISSN: 2254-3821

Year of publication: 2020

Issue: 9

Type: Article

More publications in: Biosaia: Revista de los másteres de Biotecnología Sanitaria y Biotecnología Ambiental, Industrial y Alimentaria


Motivation: Neurodegenerative diseases have become a global health problem that need more research to find a solution. Our group has described in the organism model Caenorhabditis elegans that the loss of function of the sul-2 gene, which encodes a steroid hormone sulfatase homologous STS human, improvement the symptoms of neurodegenerative diseases. Likewise, the compound STX64, an inhibitor of steroid hormone sulphatases activity, mimics the lack of sul-2 function. It has been described that ssu-1, the only C. elegans gene orthologous to human steroid hormone sulfotransferase, is expressed in ASJ amphids neurons. The initial hypothesis is to see if the improvement of the symptoms of neurodegenerative diseases in the sul-2 mutant and with the STX treatment is due to the accumulation of sulfated hormone, or on the contrary, to the decrease of the nonsulfated hormone. Methods: To analyze the expression of the ssu-1 gene in the absence of sul-2, was generated sul-2 (gk1187) V; vzEx29 [(Pssu1::GFP) + prF4 (role-6)]. To analyze the effect of the absence of sulfated hormones in the Alzheimer's model, strain GMC101, the genetic crossing between GMC 101 and ssu-1 (fc73) generated ssu-1 (fc73) V; dvls100 [unc- 54p :: A-beta-1-42: unc-54 3'UTR + mtl-2p: GFP]. Results: In the cross the strain sul-2(gk187);Pssu-1::GFP the fluorescence intensity of the ASJ amphids neurons was measured, thus quantifying the expression of the Pssu-1::GFP control as in the sul-2 mutant background. The results showed a reduction in the expression of Pssu-1 in a sul-2 mutant background, with respect to the control. While in the cross the strain ssu-1 (fc73); GMC 101 a paralysis test was carried out, seeing the percentage of paralyzed in the GMC 101 control as in the mutant with ssu1 (fc73). The results showed no significant differences between the control and the mutant. Conclusions: The reduction of the expression of the ssu-1 gene in a sul-2 mutant, suggests that the accumulation of sulfated hormones could inhibit the sulfotransferase ssu-1. This fit with a product inhibition model. On the other hand, no significant differences were observed between the GMC 101 control and the ssu-1(fc73) mutant, because the fc73 allele has a loss of sulfotransferase function, which suggests that it is the presence of sulfated hormones that have the beneficial effect.

Bibliographic References

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  • Pérez-Jiménez, M.M., et al., Steroid hormones sulfatase inactivation extends lifespan and ameliorates age-related diseases. bioRxiv, 2019: p. 541730.