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DJ-1 and prevention of oxidative stress in Parkinson's disease and other age-related disorders

Kahle, Philipp J. ; Waak, Jens ; Gasser, Thomas

Free radical biology & medicine, 2009-11, Vol.47 (10), p.1354-1361 [Periódico revisado por pares]

United States: Elsevier Inc

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Título:
DJ-1 and prevention of oxidative stress in Parkinson's disease and other age-related disorders
Autor: Kahle, Philipp J. ; Waak, Jens ; Gasser, Thomas
Assuntos: Age Factors ; Animals ; DJ-1 ; Free radicals ; Humans ; Intracellular Signaling Peptides and Proteins - chemistry ; Intracellular Signaling Peptides and Proteins - genetics ; Intracellular Signaling Peptides and Proteins - metabolism ; Neurodegeneration ; Oncogene Proteins - chemistry ; Oncogene Proteins - genetics ; Oncogene Proteins - metabolism ; Oxidative Stress ; Parkinson Disease - genetics ; Parkinson Disease - metabolism ; Parkinson Disease - pathology ; Parkinson's disease ; Protein Deglycase DJ-1 ; Redox signaling ; Stroke - genetics ; Stroke - metabolism
É parte de: Free radical biology & medicine, 2009-11, Vol.47 (10), p.1354-1361
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Descrição: 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.
Editor: United States: Elsevier Inc
Idioma: Inglês

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DJ-1 and prevention of oxidative stress in Parkinson's disease and other age-related disorders

Kahle, Philipp J. ; Waak, Jens ; Gasser, Thomas

United States: Elsevier Inc

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