Abstract

A general hallmark of neurological diseases is the loss of redox homeostasis that triggers oxidative damages to biomolecules compromising neuronal function.

Under physiological conditions the steady-state concentrations of reactive oxygen species (ROS) and reactive nitrogen species (RNS) are finely regulated for proper cellular functions.

Reduced surveillance of endogenous antioxidant defenses and/or increased ROS/RNS production leads to oxidative stress with consequent alteration of physiological processes.

Neuronal cells are particularly susceptible to ROS/RNS due to their biochemical composition. Overwhelming evidences indicate that nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-linked pathways are involved in protective mechanisms against oxidative stress by regulating antioxidant and phase II detoxifying genes.

As such, Nrf2 deregulation has been linked to both aging and pathogenesis of many human chronic diseases, including neurodegenerative ones such as Parkinson’s disease, Alzheimer’s disease and amyotrophic lateral sclerosis.

Nrf2 activity is tightly regulated by a fine balance between positive and negative modulators. A better understanding of the regulatory mechanisms underlying Nrf2 activity could help to develop novel therapeutic interventions to prevent, slow down or possibly reverse various pathological states. To this end, microRNAs (miRs) are attractive candidates because they are linked to intracellular redox status being regulated and, post-transcriptionally, regulating key components of ROS/RNS pathways, including Nrf2.

Introduction

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) pervade a wide spectrum of biological processes; therefore, their levels are tightly regulated under normal physiological conditions. At low concentrations, some ROS/RNS function as important components of numerous signalling pathways.

Conversely, increased ROS/RNS levels can generate damage to nucleic acids, lipids and proteins, thereby contributing to cellular and tissue dysfunctions.

This latter condition, known as oxidative stress, may be created in a number of ways involving both intrinsic cellular factors (i.e., enhanced activity of ROS/ RNS-generating enzymes and/or reduced capacity of the antioxidant/detoxifying systems) and extrinsic insults (i.e., exposure to environmental agents such as xenobiotics, radiations, drugs)[…]

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