title: Oxidative stress in neurodegenerative diseases: mechanisms and therapeutic perspectives.
abstract: The incidence and prevalence of neurodegenerative diseases (ND) increase with life expectancy. This paper reviews the role of oxidative stress (OS) in ND and pharmacological attempts to fight against reactive oxygen species (ROS)-induced neurodegeneration. Several mechanisms involved in ROS generation in neurodegeneration have been proposed. Recent articles about molecular pathways involved in ROS generation were reviewed. The progress in the development of neuroprotective therapies has been hampered because it is difficult to define targets for treatment and determine what should be considered as neuroprotective. Therefore, the attention was focused on researches about pharmacological targets that could protect neurons against OS. Since it is necessary to look for genes as the ultimate controllers of all biological processes, this paper also tried to identify gerontogenes involved in OS and neurodegeneration. Since neurons depend on glial cells to survive, recent articles about the functioning of these cells in aging and ND were also reviewed. Finally, clinical trials testing potential neuroprotective agents were critically reviewed. Although several potential drugs have been screened in in vitro and in vivo models of ND, these results were not translated in benefit of patients, and disappointing results were obtained in the majority of clinical trials.
authors.affiliation: National Council for Scientific and Technological Development (CNPq), Faculty of Medicine, Federal University of Bahia, 40820-020 Salvador, BA, Brazil.
authors.forename: Ailton
authors.initials: A
authors.lastname: Melo
authors.forename: Larissa
authors.initials: L
authors.lastname: Monteiro
authors.forename: Rute M F
authors.initials: RM
authors.lastname: Lima
authors.forename: Diêgo M de
authors.initials: DM
authors.lastname: Oliveira
authors.forename: Martins D de
authors.initials: MD
authors.lastname: Cerqueira
authors.forename: Ramon S
authors.initials: RS
authors.lastname: El-Bachá
mesh_terms: D000375:Aging / Q000235:genetics; D000818:Animals; D002986:Clinical Trials as Topic; D005853:Geriatrics / Q000639:trends; D006801:Humans; D058990:Molecular Targeted Therapy; D019636:Neurodegenerative Diseases / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D017211:Treatment Failure
chemical_list: D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species