Linked Life Data

20942792

Source:http://linkedlifedata.com/resource/pubmed/id/20942792

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2010-11-12
pubmed:abstractText
Target-directed drug design, although a conceptually rational approach, is only one strategy for drug discovery. In the case of neurodegenerative diseases where molecular targets and disease mechanisms are unknown, even when specific genes are known to trigger the disease, phenotypic screening offers another approach. This review describes the establishment of phenotypic screening assays using primary neurons subjected to a disease-relevant pathophysiological stress and measuring the most important functional outcome, survival. Although a challenge both to screening teams to reproducibly produce the cells and chemists to interpret structure-activity relationships, such systems have historically identified or produced effective drugs. The primary screening assay is only the start; once hits are validated, they must be characterized using traditional target-directed or mechanism-based secondary assays to establish their selectivity, lack of side-effect liability, and eventually be shown to produce the desired effects in a preclinical animal model of the disease. These compounds then provide valuable pharmacological tools to identify neurodegenerative disease targets and mechanisms, whether or not they have all the properties required of a drug candidate.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1996-3181
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
693-700
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Phenotypic screening strategies for neurodegenerative diseases: a pathway to discover novel drug candidates and potential disease targets or mechanisms.
pubmed:affiliation
Trophos, Parc Scientifique de Luminy, Luminy Biotech Entreprises - Case 931, 13288 Marseille, France. rpruss@trophos.com
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't