Title:Oxidative Stress and Antioxidants in Neurological Diseases: Is There Still Hope?
Volume: 18
Issue: 6
Author(s): Andreia Neves Carvalho*, Omidreza Firuzi, Maria Joao Gama, Jack van Horssen and Luciano Saso
Affiliation:
- Instituto de Investigação do Medicamento (iMED.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof Gama Pinto, 1649-003, Lisboa,Portugal
Keywords:
Alzheimer`s disease, antioxidants, biomarkers, huntington`s disease, multiple sclerosis, neurodegenerative diseases, oxidative stress, parkinson`s disease
Abstract: Oxidative stress is a pathological feature common to a multitude of neurological diseases.
The production of reactive oxygen species (ROS) is the main mechanism underlying this cellular redox
imbalance. Antioxidants protect biological targets against ROS, therefore, they have been considered as
attractive potential therapeutic agents to counteract ROS-mediated neuronal damage. However, despite
encouraging in vitro and preclinical in vivo data, the clinical efficacy of antioxidant treatment strategies
is marginal and most clinical trials using antioxidants as therapeutic agents in neurodegenerative diseases
have yielded disappointing outcomes. This might in part be due to the need of adjustment in concentrations
and time parameters between preclinical studies and clinical settings. Moreover new efficient
delivery methods need to be investigated, particularly taking into account that a successful therapeutic
agent for neurological diseases should readily cross the blood-brain barrier (BBB). In that sense,
the use of compounds that cross the BBB and boost the endogenous antioxidant defense machinery, by
activating for instance the Nrf2 pathway, or compounds that are able to modulate ROS production, such
as NOX enzyme inhibitors, seems to represent a more promising approach to combat oxidative stress in
the central nervous system (CNS). Here we present a brief overview of the main players in oxidative
stress and outline evidences of their involvement in Parkinson's disease, Alzheimer's disease,
Huntington's disease and multiple sclerosis. Finally, we review and critically discuss the potential of antioxidants
as therapeutics for central nervous system disorders with a special focus on emerging novel
therapeutic strategies.
