Linked Life Data

20333559

Source:http://linkedlifedata.com/resource/pubmed/id/20333559

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2-3
pubmed:dateCreated
2010-5-26
pubmed:abstractText
Overstimulation of N-methyl-D-aspartate (NMDA)-type glutamate receptors accounts, at least in part, for excitotoxic neuronal damage, potentially contributing to a wide range of acute and chronic neurologic diseases. Neurodegenerative disorders including Alzheimer's disease (AD) and Parkinson's disease (PD), manifest deposits of misfolded or aggregated proteins, and result from synaptic injury and neuronal death. Recent studies have suggested that nitrosative stress due to generation of excessive nitric oxide (NO) can mediate excitotoxicity in part by triggering protein misfolding and aggregation, and mitochondrial fragmentation in the absence of genetic predisposition. S-Nitrosylation, or covalent reaction of NO with specific protein thiol groups, represents a convergent signal pathway contributing to NO-induced protein misfolding and aggregation, compromised dynamics of mitochondrial fission-fusion process, thus leading to neurotoxicity. Here, we review the effect of S-nitrosylation on protein function under excitotoxic conditions, and present evidence suggesting that NO contributes to protein misfolding and aggregation via S-nitrosylating protein-disulfide isomerase or the E3 ubiquitin ligase parkin, and mitochondrial fragmentation through beta-amyloid-related S-nitrosylation of dynamin-related protein-1. Moreover, we also discuss that inhibition of excessive NMDA receptor activity by memantine, an uncompetitive/fast off-rate (UFO) drug can ameliorate excessive production of NO, protein misfolding and aggregation, mitochondrial fragmentation, and neurodegeneration.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1559-1182
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
41
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
55-72
pubmed:meshHeading
pubmed-meshheading:20333559-Animals, pubmed-meshheading:20333559-Calcium, pubmed-meshheading:20333559-Cell Death, pubmed-meshheading:20333559-Dynamins, pubmed-meshheading:20333559-Glutamic Acid, pubmed-meshheading:20333559-Humans, pubmed-meshheading:20333559-Mitochondria, pubmed-meshheading:20333559-Nerve Tissue Proteins, pubmed-meshheading:20333559-Neurodegenerative Diseases, pubmed-meshheading:20333559-Nitric Oxide, pubmed-meshheading:20333559-Oxidation-Reduction, pubmed-meshheading:20333559-Protein Disulfide-Isomerases, pubmed-meshheading:20333559-Protein Folding, pubmed-meshheading:20333559-Reactive Nitrogen Species, pubmed-meshheading:20333559-Reactive Oxygen Species, pubmed-meshheading:20333559-Receptors, N-Methyl-D-Aspartate, pubmed-meshheading:20333559-Signal Transduction, pubmed-meshheading:20333559-Stress, Physiological, pubmed-meshheading:20333559-Ubiquitin-Protein Ligases
pubmed:year
2010
pubmed:articleTitle
Redox reactions induced by nitrosative stress mediate protein misfolding and mitochondrial dysfunction in neurodegenerative diseases.
pubmed:affiliation
Department of Pathology and Anatomical Sciences, University of Missouri-Columbia School of Medicine, One Hospital Drive, Columbia, MO 65212, USA. guze@health.missouri.edu
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural