Linked Life Data

21715656

Source:http://linkedlifedata.com/resource/pubmed/id/21715656

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
29
pubmed:dateCreated
2011-7-20
pubmed:abstractText
Due to the lack of relevant animal models, development of effective treatments for human mitochondrial diseases has been limited. Here we establish a rapid, yeast-based assay to screen for drugs active against human inherited mitochondrial diseases affecting ATP synthase, in particular NARP (neuropathy, ataxia, and retinitis pigmentosa) syndrome. This method is based on the conservation of mitochondrial function from yeast to human, on the unique ability of yeast to survive without production of ATP by oxidative phosphorylation, and on the amenability of the yeast mitochondrial genome to site-directed mutagenesis. Our method identifies chlorhexidine by screening a chemical library and oleate through a candidate approach. We show that these molecules rescue a number of phenotypes resulting from mutations affecting ATP synthase in yeast. These compounds are also active on human cybrid cells derived from NARP patients. These results validate our method as an effective high-throughput screening approach to identify drugs active in the treatment of human ATP synthase disorders and suggest that this type of method could be applied to other mitochondrial diseases.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1091-6490
pubmed:author
pubmed:issnType
Electronic
pubmed:day
19
pubmed:volume
108
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
11989-94
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
A yeast-based assay identifies drugs active against human mitochondrial disorders.
pubmed:affiliation
INSERM U613; Université de Brest, Faculté de Médecine et des Sciences de la Santé; Etablissement Français du Sang (EFS) Bretagne; Centre Hospitalier Régional Universitaire Brest, Hop Morvan, Laboratoire de Génétique Moléculaire, F-29200 Brest, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't