Vallese · 2025 · Redox biology
Different NRF2 response in patient-derived cells
Did ASD-derived cells show the same antioxidant response to sulforaphane?
In vitro · patient-derived skin fibroblasts
Key findings
Defense responses in patient-derived cells
ASD-derived skin cells had higher baseline NRF2 activity and BACH1 accumulation, with a weaker HO1 response. After sulforaphane stimulation, NRF2 nuclear translocation and HO1 induction did not rise as much as in comparator cells.
Results of hemin treatment
Restoration of HO1 and mitochondrial measures was observed with hemin, which was tested separately.
Detailed results
Higher NRF2 activity and lower HO1 expression
Skin fibroblasts from five people with ASD and four comparators were cultured. Baseline NRF2 activity was higher in ASD-derived cells, but expression of the downstream protective enzyme HO1 was lower. Nuclear accumulation of BACH1, a transcriptional repressor, was also higher.
The researchers examined differences in regulation among NRF2 activity, BACH1 accumulation, and HO1 responses.
Different responses to sulforaphane and hemin
With timed 10 µM sulforaphane treatment, ASD-derived cells did not increase NRF2 nuclear translocation sufficiently compared with comparator cells. Separately, the researchers applied hemin, which promotes BACH1 export from the nucleus and degradation.
| Treatment compound | Findings in ASD-derived cells |
|---|---|
| Sulforaphane | Limited NRF2 nuclear translocation and downstream defense response |
| Hemin · separate experiment | Reduced BACH1, restored HO1, and improvements in some mitochondrial measures |
Results from cell cultures treated separately with the two compounds.
Differences in responses of donor-derived cells
Differences in sulforaphane responses were observed in skin cells from a small number of donors. The researchers proposed differences in regulation of cellular antioxidant pathways as a topic for follow-up research.
Study design
The NRF2, KEAP1, and BACH1 pathways were compared in cells cultured from skin samples. Gene, protein, and mitochondrial measures were assessed after SFN stimulation and separate hemin stimulation.
- Participants
- Skin fibroblast cultures from five people with ASD and four comparators
- Intake and observation
- SFN 10 µM · timed cell treatment
Separate hemin treatment experiment - Measures
- NRF2 nuclear translocation, HO1 expression, BACH1, and mitochondrial measures
Study context
The study cultured skin cells from five people with ASD and four comparators, treating them separately with sulforaphane and hemin to compare responses.
Original paper and sources
Deregulated Nrf2-Keap1-BACH1 axis in autism spectrum disorder.
- Journal
- Redox biology · 2025 · 86: 103837
- First published
- 2025-08-21