| Poly(ADP-ribose) metabolism in brain and its role in ischemia pathology. | |
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MedLine Citation:
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PMID: 20411356 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The biological roles of poly(ADP-ribose) polymers (PAR) and poly(ADP-ribosyl)ation of proteins in the central nervous system are diverse. The homeostasis of PAR orchestrated by poly(ADP-ribose) polymerase-1 (PARP-1) and poly(ADP-ribose) glycohydrolase (PARG) is crucial for cell physiology and pathology. Both enzymes are ubiquitously distributed in neurons and glia; however, they are segregated at the subcellular level. PARP-1 serves as a "nick sensor" for single- or double-stranded breaks in DNA and is involved in long and short patch base-excision repair, while PARG breaks down PAR. The stimulation of PARP-1 and PAR formation can activate proinflammatory transcription factors, including nuclear factor kappa B. However, hyperactivation of PARP-1 can result in depletion of NAD/ATP, and in PAR-dependent mitochondrial pore formation leading to release of apoptosis inducing factor and cell death. The role of PAR as a death signaling molecule in brain ischemia-reperfusion and inflammation as well as the effect of gender and aging is presented in this review. Modulating the PAR level through pharmacological or genetic intervention on PARP-1/PARG activity and gene expression should be a valuable way for neuroprotective strategy. |
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Authors:
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Robert Piotr Strosznajder; Kinga Czubowicz; Henryk Jesko; Joanna Benigna Strosznajder |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Review Date: 2010-04-23 |
Journal Detail:
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Title: Molecular neurobiology Volume: 41 ISSN: 1559-1182 ISO Abbreviation: Mol. Neurobiol. Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-05-26 Completed Date: 2010-10-08 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8900963 Medline TA: Mol Neurobiol Country: United States |
Other Details:
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Languages: eng Pagination: 187-96 Citation Subset: IM |
Affiliation:
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Department of Neurosurgery, Mossakowski Medical Research Centre, Polish Academy of Sciences, 5 Pawinskiego St., 02-106, Warsaw, Poland. roberts@cmdik.pan.pl |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Aging
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physiology Animals Brain / metabolism*, pathology* Brain Ischemia / metabolism*, pathology* Glycoside Hydrolases / metabolism Humans Mitochondria / metabolism Poly Adenosine Diphosphate Ribose / metabolism* Poly(ADP-ribose) Polymerases / metabolism Reactive Oxygen Species / metabolism Signal Transduction / physiology |
| Chemical | |
Reg. No./Substance:
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0/Reactive Oxygen Species; 26656-46-2/Poly Adenosine Diphosphate Ribose; EC 2.4.2.30/PARP1 protein, human; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 3.2.1.-/Glycoside Hydrolases; EC 3.2.1.143/poly ADP-ribose glycohydrolase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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