Erucin, a Natural Isothiocyanate, Prevents Polyglutamine-Induced Toxicity in Caenorhabditis elegans via aak-2/AMPK and daf-16/FOXO Signaling

Fecha de publicación: 01/11/2024

Autores de IIS La Fe

• Andrea Del Valle Carranza Figuerca

  Autor

• Rafael Vázquez Manrique

  Autor

Participantes ajenos a IIS La Fe

• Balducci, Martina
• Perez, Julia Tortajada
• del Rio, Cristina Trujillo
• Perez, Mar Collado
• Escribano, Ana Pilar Gomez
• Tarozzi, Andrea

Grupos

• Biomedicina Molecular, Celular y Genómica

  

  Leader

  José María Millán Salvador

• Unidad mixta de investigación en enfermedades raras (CIPF)

  

  Leader

  José María Millán Salvador

Abstract

Several neurodegenerative diseases (NDDs), such as Huntington's disease, six of the spinocerebellar ataxias, dentatorubral-pallidoluysian atrophy, and spinobulbar muscular atrophy, are caused by abnormally long polyglutamine (polyQ) tracts. Natural compounds capable of alleviating polyQ-induced toxicity are currently of great interest. In this work, we investigated the modulatory effect against polyQ neurotoxic aggregates exerted by erucin (ERN), an isothiocyanate naturally present in its precursor glucoerucin in rocket salad leaves and in its oxidized form, sulforaphane (SFN), in broccoli. Using C. elegans models expressing polyQ in different tissues, we demonstrated that ERN protects against polyQ-induced toxicity and that its action depends on the catalytic subunit of AMP-activated protein kinase (aak-2/AMPK alpha 2) and, downstream in this pathway, on the daf-16/FOXO transcription factor, since nematodes deficient in aak-2/AMPK alpha 2 and daf-16 did not respond to the treatment, respectively. Although triggered by a different source of neurotoxicity than polyQ diseases, i.e., by alpha-synuclein (alpha-syn) aggregates, Parkinson's disease (PD) was also considered in our study. Our results showed that ERN reduces alpha-syn aggregates and slightly improves the motility of worms. Therefore, further preclinical studies in mouse models of protein aggregation are justified and could provide insights into testing whether ERN could be a potential neuroprotective compound in humans.

Keywords

• erucin; <italic>Caenorhabditis elegans</italic>; neuroprotection; polyQ toxicity; AMPK; <italic>daf-16</italic>/FOXO