SOD1 and DJ-1 Converge at Nrf2 Pathway : A Clue for Antioxidant Therapeutic Potential in Neurodegeneration

Abstract EN

Neurodegenerative diseases share diverse pathological features and among these oxidative stress (OS) plays a leading role.

Impaired activity and reduced expression of antioxidant proteins have been reported as common events in several aging-associated disorders.

In this review paper, we first provide an overview of the involvement of reactive oxygen species- (ROS-) induced oxidative damage in Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS).

Subsequently, we focus on DJ-1 and SOD1 proteins, which are involved in PD and ALS and also exert a prominent role in the interaction between redox homeostasis and neurodegeneration.

Interestingly, recent studies demonstrated that DJ-1 and SOD1 are both tightly connected with Nrf2 protein, a transcriptional factor and master regulator of the expression of many antioxidant/detoxification genes.

Nrf2 is emerging as a key neuroprotective protein in neurodegenerative diseases, since it helps neuronal cells to cope with toxic insults and OS.

We herein summarize the recent literature providing a detailed picture of the promising therapeutic efficacy of Nrf2 natural and synthetic inducers as disease-modifying molecules for the treatment of neurodegenerative diseases.