Genetic overactivation of Nrf2: consequences and treatment

This review describes the consequences of chronic activation of Nrf2 (due to genetic mutation in this protein).

Low homocysteine is noted. I saw a few results of children with ASD and tics that have low homocysteine - presumably because of upregulated transsulfuration pathway or low intake of methionine in the diet.

Treatment is also mentioned in the paper: Luteolin (nrf2 inhibitor) and ascorbic acid (vitamin C; also inhibits Nrf2).

Somatic mutations of NFE2L2 leading to NRF2 accumulation promote cell survival and drug resistance in cancer cells. Here we show that the same mutations as inborn de novo mutations cause an early onset multisystem disorder with failure to thrive, immunodeficiency and neurological symptoms.

NRF2 accumulation leads to widespread misregulation of gene expression and an imbalance in cytosolic redox balance.

The unique combination of white matter lesions, hypohomocysteinaemia and increased G-6-P-dehydrogenase activity will facilitate early diagnosis and therapeutic intervention of this novel disorder. (R1)