Linked Life Data

17503736

Source:http://linkedlifedata.com/resource/pubmed/id/17503736

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2007-5-16
pubmed:abstractText
The dogma that the adult central nervous system (CNS) is nonpermissive to axonal regeneration is beginning to fall in the face of increased understanding of the molecular and cellular biology of axon outgrowth. It is now appreciated that axon growth is regulated by a combination of extracellular factors related to the milieu of the developing or adult CNS and the presence of injury, and intracellular factors related to the "growth state" of the developing or regenerating neuron. Several critical points of convergence within the developing or regenerating neuron for mediating intracellular cell signaling effects on the growth cone cytoskeleton have been identified, and their modulation has produced marked increases in axon outgrowth within the "nonpermissive" milieu of the adult injured CNS. One such critical convergence point is the small GTPase RhoA, which integrates signaling events produced by both myelin-associated inhibitors (e.g., NogoA) and astroglial-derived inhibitors (chondroitin sulfate proteoglycans) and regulates the activity of downstream effectors that modulate cytoskeletal dynamics within the growth cone mediating axon outgrowth or retraction. Inhibition of RhoA has been associated with increased outgrowth on nonpermissive substrates in vitro and increased axon regeneration in vivo. We are developing lentiviral vectors that modulate RhoA activity, allowing more long-term expression than is possible with current approaches. These vectors may be useful in regenerative strategies for spinal cord injury, brain injury, and neurodegenerative diseases including Parkinson's disease, Alzheimer's disease, and Huntington's disease.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0963-6897
pubmed:author
pubmed:issnType
Print
pubmed:volume
16
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
245-62
pubmed:dateRevised
2007-12-3
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
The pivotal role of RhoA GTPase in the molecular signaling of axon growth inhibition after CNS injury and targeted therapeutic strategies.
pubmed:affiliation
Department of Neurosurgery, Center for Neurodegenerative Diseases, Emory University School of Medicine, Atlanta, GA 30322, USA. Robert.gross@emoryhealthcare.org
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural