کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1909722 | 1046738 | 2009 | 8 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: DJ-1 and prevention of oxidative stress in Parkinson's disease and other age-related disorders DJ-1 and prevention of oxidative stress in Parkinson's disease and other age-related disorders](/preview/png/1909722.png)
Mutations in the PARK7/DJ-1 gene are rare causes of autosomal-recessive hereditary Parkinson's disease. Loss-of-function mutations lead to the characteristic selective neurodegeneration of nigrostriatal dopaminergic neurons, which accounts for parkinsonian symptoms. Originally identified as an oncogene, DJ-1 is a ubiquitous redox-responsive cytoprotective protein with diverse functions. In addition to cell-autonomous neuroprotective roles, DJ-1 may act in a transcellular manner, being up-regulated in reactive astrocytes in chronic neurodegenerative diseases as well as in stroke. Thus, DJ-1, particularly in its oxidized form, has been recognized as a biomarker for cancer and neurodegenerative diseases. The crystal structure of DJ-1 has been solved, allowing detailed investigations of the redox-reactive center of DJ-1. Structure–function studies revealed that DJ-1 may become activated in the presence of reactive oxygen species, under conditions of oxidative stress, but also as part of physiological receptor-mediated signal transduction. DJ-1 regulates redox signaling kinase pathways and acts as a transcriptional regulator of antioxidative gene batteries. Therefore, DJ-1 is an important redox-reactive signaling intermediate controlling oxidative stress after ischemia, upon neuroinflammation, and during age-related neurodegenerative processes. Augmenting DJ-1 activity might provide novel approaches to treating chronic neurodegenerative illnesses such as Parkinson's disease and acute damage such as stroke.
Journal: Free Radical Biology and Medicine - Volume 47, Issue 10, 15 November 2009, Pages 1354–1361