Please use this identifier to cite or link to this item: https://hdl.handle.net/10316/106529
Title: Oxidative Stress in Amyotrophic Lateral Sclerosis: Pathophysiology and Opportunities for Pharmacological Intervention
Authors: Cunha-Oliveira, Teresa 
Montezinho, Liliana 
Mendes, Catarina
Firuzi, Omidreza
Saso, Luciano
Oliveira, Paulo J. 
Silva, Filomena S. G. 
Issue Date: 2020
Publisher: Hindawi
Project: PTDC/ MED-FAR/29391/2017 
POCI-01-0145-FEDER-029391 
PTDC/BTM-SAL/29297/2017 
POCI-01-0145- FEDER-029297 
UIDB/04539/2020 
Serial title, monograph or event: Oxidative Medicine and Cellular Longevity
Volume: 2020
Abstract: Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease or Charcot disease, is a fatal neurodegenerative disease that affects motor neurons (MNs) and leads to death within 2-5 years of diagnosis, without any effective therapy available. Although the pathological mechanisms leading to ALS are still unknown, a wealth of evidence indicates that an excessive reactive oxygen species (ROS) production associated with an inefficient antioxidant defense represents an important pathological feature in ALS. Substantial evidence indicates that oxidative stress (OS) is implicated in the loss of MNs and in mitochondrial dysfunction, contributing decisively to neurodegeneration in ALS. Although the modulation of OS represents a promising approach to protect MNs from degeneration, the fact that several antioxidants with beneficial effects in animal models failed to show any therapeutic benefit in patients raises several questions that should be analyzed. Using specific queries for literature search on PubMed, we review here the role of OS-related mechanisms in ALS, including the involvement of altered mitochondrial function with repercussions in neurodegeneration. We also describe antioxidant compounds that have been mostly tested in preclinical and clinical trials of ALS, also describing their respective mechanisms of action. While the description of OS mechanism in the different mutations identified in ALS has as principal objective to clarify the contribution of OS in ALS, the description of positive and negative outcomes for each antioxidant is aimed at paving the way for novel opportunities for intervention. In conclusion, although antioxidant strategies represent a very promising approach to slow the progression of the disease, it is of utmost need to invest on the characterization of OS profiles representative of each subtype of patient, in order to develop personalized therapies, allowing to understand the characteristics of antioxidants that have beneficial effects on different subtypes of patients.
URI: https://hdl.handle.net/10316/106529
ISSN: 1942-0994
1942-0900
DOI: 10.1155/2020/5021694
Rights: openAccess
Appears in Collections:I&D CNC - Artigos em Revistas Internacionais

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