Our results indicated that KT can protect HT22 cells from glutamate-induced cell death by activating Nrf2 pathway and inducing expression of HO-1, suggesting KT might be a drug candidate for treatment of AD and other neurodegenerative disorders related to oxidative stress.
These observations suggest HO-1 pathway as a cellular effector in the mechanism by which resveratrol protects astroglial cells against GSH depletion, a condition that may be associated to neurodegenerative diseases.
Therefore, targeted suppression of glial HO-1 hyperactivity may prove to be a rational and effective therapeutic intervention in AD and related neurodegenerative disorders.
Oxidative stress is implicated in Parkinson's disease (PD) and Alzheimer's disease (AD), and heme oxygenase-1 (HO-1) is a potent antioxidant overexpressed in PD substantia nigra and AD cerebral cortex and hippocampus, indicating a possible up-regulation of antioxidant defenses in both neurodegenerative diseases.
Collectively, our findings suggest that HO-1 over-expression contributes to the pathological iron deposition and mitochondrial damage documented in these aging-related neurodegenerative disorders.
Activation of this HO-1-MnSOD axis may play an important role in the pathogenesis of Alzheimer disease, Parkinson disease and other free radical-related neurodegenerative disorders.