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.

Mitigation of ROS Insults by Streptomyces Secondary Metabolites in Primary Cortical Neurons

“…As a result of this lack of balance, a mitochondrial dysfunction and an elevation of free radical levels take place with the consequent cellular damage. 1,9 We report here that several of the compounds tested were able to protect primary cortical neurons against H 2 O 2 insult, assessed by measurements of mitochondrial activity (function and membrane potential) or intracellular ROS levels, and improvement of the depressed antioxidant molecules CAT and GSH. Most of them, that is, compounds A, B, C, E, and F diminished intracellular ROS production when primary cortical neurons were incubated with H 2 O 2 and all of them, except compound A, also inhibited H 2 O 2 effect over mitochondrial function.…”

Stimulus-dependent neuronal cell responses in SH-SY5Y neuroblastoma cells

“…Abnormal neuronal cell death in the central nervous system (CNS) is also associated with acute neurological injury, such as cerebral ischemia and trauma, as well as chronic neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease (PD). Excitatory neurotransmitter-induced neurotoxicity, neurotoxins, and oxidative stress are commonly used to induce neuronal cell death in in vivo and in vitro models (2)(3)(4).…”

Effect of the Lipid Peroxidation Product 4-Hydroxynonenal on Neuroinflammation in Microglial Cells: Protective Role of Quercetin and Monochloropivaloylquercetin

“…26,27 The ability of HNE to exert a number of toxicological effects has been attributed to its electrophilic α, β-unsaturated carbonyl moiety that can react through 1, 2 and 1, 4 additions with nucleophiles such as cysteine, lysine, and histidine residues. 28,29 The normal, physiological level of HNE in human tissues and plasma range from 0.07 to 2.8 μM, while in diseased states and near the core of lipid peroxidation sites, its concentration can be greatly increased (even above 100 μM). 30 Treatment with low (1 and 10 μM) concentrations of HNE caused significant induction of cell death.…”