title: Thiol-redox signaling, dopaminergic cell death, and Parkinson's disease.
abstract: CONCLUSIONS
  Parkinson's disease (PD) is characterized by the selective loss of dopaminergic neurons of the substantia nigra pars compacta, which has been widely associated with oxidative stress. However, the mechanisms by which redox signaling regulates cell death progression remain elusive.
  
  
  BACKGROUND
  Early studies demonstrated that depletion of glutathione (GSH), the most abundant low-molecular-weight thiol and major antioxidant defense in cells, is one of the earliest biochemical events associated with PD, prompting researchers to determine the role of oxidative stress in dopaminergic cell death. Since then, the concept of oxidative stress has evolved into redox signaling, and its complexity is highlighted by the discovery of a variety of thiol-based redox-dependent processes regulating not only oxidative damage, but also the activation of a myriad of signaling/enzymatic mechanisms.
  
  
  RESULTS
  GSH and GSH-based antioxidant systems are important regulators of neurodegeneration associated with PD. In addition, thiol-based redox systems, such as peroxiredoxins, thioredoxins, metallothioneins, methionine sulfoxide reductases, transcription factors, as well as oxidative modifications in protein thiols (cysteines), including cysteine hydroxylation, glutathionylation, and nitrosylation, have been demonstrated to regulate dopaminergic cell loss.
  
  
  CONCLUSIONS
  In this review, we summarize major advances in the understanding of the role of thiol-redox signaling in dopaminergic cell death in experimental PD. Future research is still required to clearly understand how integrated thiol-redox signaling regulates the activation of the cell death machinery, and the knowledge generated should open new avenues for the design of novel therapeutic approaches against PD.
authors.affiliation: Redox Biology Center and School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USA.
authors.forename: Aracely
authors.initials: A
authors.lastname: Garcia-Garcia
authors.forename: Laura
authors.initials: L
authors.lastname: Zavala-Flores
authors.forename: Humberto
authors.initials: H
authors.lastname: Rodriguez-Rocha
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Franco
mesh_terms: D000818:Animals; D016923:Cell Death / Q000235:genetics / Q000502:physiology*; D059290:Dopaminergic Neurons / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D010084:Oxidation-Reduction; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D013438:Sulfhydryl Compounds / Q000378:metabolism*
chemical_list: D013438:Sulfhydryl Compounds