Abstract
Public concerns over the use of synthetic pesticides are growing since many studies have shown their impact on human health. A new environmental movement in occidental countries promoting an organic agriculture favours the rebirth of botanical pesticides. These products confer an effective alternative to chemical pesticides such as glyphosate. Among the biopesticides, the α-terthienyls found in the roots of Tagetes species, are powerful broad-spectrum pesticides. We found that an α-terthienyl analogue with herbicidal properties, called A6, triggers resistant SDS oligomers of the pathogenic prion protein PrPSc (rSDS-PrPSc) in cells. Our main question is to determine if we can induce those rSDS-PrPSc oligomers in vitro and in vivo, and their impact on prion aggregation and propagation. Using wild-type mice challenged with prions, we showed that A6 accelerates or slows down prion disease depending on the concentration used. At 5 mg/kg, A6 is worsening the pathology with a faster accumulation of PrPSc, reminiscent to soluble toxic rSDS-PrPSc oligomers. In contrast, at 10 and 20 mg/kg of A6, prion disease occurred later, with less PrPSc deposits and with rSDS-PrPSc oligomers in the brain reminiscent to non-toxic aggregates. Our results are bringing new openings regarding the impact of biopesticides in prion and prion-like diseases.
Highlights
With the increase of life expectancy in the developed countries, the prevalence of age-related disorders continues to rise
The results showed that P30, one of the lead compounds identified is able to induce a strong signal of proteinase K (PK) rSDS-PrPSc oligomers, as well as A6 and MR100, in a lesser extend due to their ability to precipitate prions in the tubes
A new environmental movement in the occidental countries, promoting an organic agriculture has allowed the use of some botanical pest control and favoured the rebirth of botanical biopesticides[19]
Summary
With the increase of life expectancy in the developed countries, the prevalence of age-related disorders continues to rise. In a drug screening assay on prion-infected cells, that a compound, called A6 is a strong inducer of SDS-resistant oligomers of the pathogenic form of the prion protein PrPSc (rSDS-PrPSc)[15,16] This compound was previously described for its herbicidal activity[17] and is structurally related to the family of α-terthienyls (α-Ter), natural molecules synthesized by plants such as marigolds and Asteraceae[18]. In vitro and in vivo exposures to low doses of A6 are likely more prone to induce soluble toxic species leading to shorter survival life in the exposed animals These results are bringing new openings regarding the potential impact of biopesticides in prion and prion-like diseases
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have