This study provides a first mechanistic explanation for the key regulatory role of Trx1 as a gatekeeper in activation of CASP6 and induction of nuclear invagination, an important player in ND pathophysiology.
Therefore, our results suggest that the TXNIP-Trx-TrxR redox pathway may participate in RPE dysfunction in DR and other retinal neurodegenerative diseases.
In the present study, grape seed proanthocyanidin extract (GSPE) was used to upregulate the expression of thioredoxin (Trx), in order to evaluate its potential as a novel agent for the prevention and treatment of neurodegenerative diseases, including diabetic retinopathy.
This study identifies ASK1/JNK and ASK1/p38 as two critical pathways involved in the activation of cell death under oxidative stress conditions and identifies the Nrf2/Trx axis as a new target to block these pathways and protect from oxidant exposure such as that found in Parkinson and other neurodegenerative diseases.
Taken together, these data suggest that DHEA may be useful in treating age-related neurodegenerative diseases based on its up-regulating effects on an antioxidant and neuroprotective protein thioredoxin, a substrate in the Trx redox system.