Oxidative stress and the pathogenesis of neurodegenerative disorders.
Microglia-derived inflammatory neurotoxins play a principal role in the pathogenesis of neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and HIV-associated dementia; chief among these is reactive oxygen species. The detrimental effects of oxidative stress in the brain and nervous system are primarily a result of the diminished capacity of the central nervous system to prevent ongoing oxidative damage. A spectrum of environmental cues, mitochondrial dysfunction, accumulation of aberrant misfolded proteins, inflammation, and defects in protein clearance are known to evolve and form as a result of disease progression. These factors likely affect glial function serving to accelerate the tempo of disease. Understanding the relationships between disease progression, free radical formation, neuroinflammation, and neurotoxicity is critical to elucidating disease mechanisms and the development of therapeutic modalities to combat disease processes. In an era where populations continue to age, the prevalence and incidence of age-related neurodegenerative diseases are on the rise; therefore, the need for novel therapeutic strategies that attenuate neuroinflammation and protect neurons against oxidative stress is ever more immediate.
Department of Pharmacology and Experimental Neuroscience, Center for Neurovirology and Neurodegenerative Disorders, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA.
Ashley
A
Reynolds
Chad
C
Laurie
R Lee
RL
Mosley
Howard E
HE
Gendelman
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000975:Antioxidants / Q000627:therapeutic use; D005609:Free Radicals; D018698:Glutamic Acid / Q000502:physiology; D005973:Glutamine / Q000502:physiology; D005978:Glutathione / Q000502:physiology; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology; D008262:Macrophage Activation / Q000502:physiology; D017628:Microglia / Q000502:physiology; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D005609:Free Radicals; D007155:Immunologic Factors; D036341:Intercellular Signaling Peptides and Proteins; D005973:Glutamine; D018698:Glutamic Acid; D005978:Glutathione