title: Oxidative stress-induced signaling pathways implicated in the pathogenesis of Parkinson's disease.
abstract: Parkinson's disease is the second most common neurodegenerative movement disorder; however, its etiology remains elusive. Nevertheless, in vivo observations have concluded that oxidative stress is one of the most common causes in the pathogenesis of Parkinson's disease. It is known that mitochondria play a crucial role in reactive oxygen species-mediated pathways, and several gene products that associate with mitochondrial function are the subject of Parkinson's disease research. The PTEN-induced kinase 1 (PINK1) protects cells from mitochondrial dysfunction and is linked to the autosomal recessive familial form of the disease. PINK1 is a key player in many signaling pathways engaged in mitophagy, apoptosis, or microglial inflammatory response and is induced by oxidative stress. Several proteins participate in mitochondrial networks, and they are associated with PINK1. The E3 ubiquitin ligase Parkin, the protease presenilin-associated rhomboid-like serine protease, the tyrosine kinase c-Abl, the protein kinase MARK2, the protease HtrA2, and the tumor necrosis factor receptor-associated protein 1 (TRAP1) provide different steps of control in protection against oxidative stress. Furthermore, environmental toxins, such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, have been identified as contributors to parkinsonism by increasing oxidative stress in dopaminergic neurons. The present review discusses the mechanisms and effects of oxidative stress, the emerging concept of the impact of environmental toxins, and a possible neuroprotective role of the antioxidant astaxanthin in various neurodegenerative disorders with particular emphasis in Parkinson's disease.
authors: Laboratory of Cellular and Molecular Neurobiology, Department of Biochemistry, Hellenic Pasteur Institute, 11521, Athens, Greece.
authors: Georgia S
authors: GS
authors: Gaki
authors: Athanasios G
authors: AG
authors: Papavassiliou
mesh_terms: D000818:Animals; D017209:Apoptosis; D001479:Basal Ganglia / Q000378:metabolism / Q000473:pathology; D020013:Calcium Signaling; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism; D029721:Drosophila Proteins / Q000502:physiology; D004331:Drosophila melanogaster; D006801:Humans; D045726:Metalloproteases / Q000235:genetics / Q000502:physiology; D019216:Metals, Heavy / Q000009:adverse effects; D017628:Microglia / Q000502:physiology; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics / Q000502:physiology; D008959:Models, Neurological; D018696:Neuroprotective Agents / Q000627:therapeutic use; D009498:Neurotoxins / Q000633:toxicity; D018384:Oxidative Stress; D010300:Parkinson Disease / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D020734:Parkinsonian Disorders / Q000235:genetics / Q000378:metabolism; D011494:Protein Kinases / Q000235:genetics / Q000502:physiology; D016315:Proto-Oncogene Proteins c-abl / Q000502:physiology; D017470:Receptors, Glutamate / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000502:physiology; D024341:Xanthophylls / Q000627:therapeutic use; D000099202:PTEN-Induced Putative Kinase
chemical_list: D029721:Drosophila Proteins; D045726:Metalloproteases; D019216:Metals, Heavy; D024101:Mitochondrial Proteins; D018696:Neuroprotective Agents; D009498:Neurotoxins; D011494:Protein Kinases; D016315:Proto-Oncogene Proteins c-abl; D017470:Receptors, Glutamate; D044767:Ubiquitin-Protein Ligases; D024341:Xanthophylls; D000099202:PTEN-Induced Putative Kinase; C005948:astaxanthine; C111567:parkin protein; C485223:PARL protein, human