Show simple item record

dc.contributor.authorKeowkase, Roongpetch
dc.contributor.authorAboukhatwa, Marwa
dc.contributor.authorAdam, Bao-Ling
dc.contributor.authorBeach, J Warren
dc.contributor.authorTerry, Alvin V Jr
dc.contributor.authorBuccafussco, Jerry J
dc.contributor.authorLuo, Yuan
dc.date.accessioned2013-06-12T15:01:35Z
dc.date.available2013-06-12T15:01:35Z
dc.date.issued2010-12-16
dc.identifier.citationMolecular Neurodegeneration. 2010 Dec 16;5(1):59
dc.identifier.urihttp://dx.doi.org/10.1186/1750-1326-5-59
dc.identifier.urihttp://hdl.handle.net/10724/19653
dc.description.abstractAbstract Background Our previous work indicated that novel analogs of choline have cytoprotective effects in vitro that might be useful in neurodegenerative conditions such as Alzheimer's disease (AD). Furthermore, two lead compounds (JWB1-84-1 and JAY2-22-33) from a library of more than 50 improved cognitive performances in a transgenic mouse model of AD. The purpose of these experiments was to more specifically investigate the neuroprotective capabilities of these lead compounds both in vitro and in vivo. Results We used N2a cells which express a Swedish mutation in the amyloid precursor protein and presenilin 1 genes to investigate the effect of JWB1-84-1 and JAY2-22-33 on β-amyloid (Aβ) levels and found that both compounds significantly reduced Aβ levels. JWB1-84-1 and JAY2-22-33 also protected rat primary cortical neurons from Aβ toxicity. Subsequently, we utilized the nematode Caenorhabditis elegans (C. elegans) as an in vivo model organism to identify potential molecular targets of these compounds. In the C. elegans model of Aβ toxicity, human Aβ is expressed intracellularly in the body wall muscle. The expression and subsequent aggregation of Aβ in the muscle leads to progressive paralysis. Conclusion We found that JAY2-22-33 (but not JWB1-84-1) significantly reduced Aβ toxicity by delaying paralysis and this protective effect required both the insulin signaling pathway and nicotinic acetylcholine receptors (nAChRs).
dc.titleNeuroprotective effects and mechanism of cognitive-enhancing choline analogs JWB 1-84-1 and JAY 2-22-33 in neuronal culture and Caenorhabditis elegans
dc.typeJournal Article
dc.date.updated2013-06-07T16:48:09Z
dc.description.versionPeer Reviewed
dc.language.rfc3066en
dc.rights.holderRoongpetch Keowkase et al.; licensee BioMed Central Ltd.


Files in this item

Thumbnail
Thumbnail

This item appears in the following Collection(s)

Show simple item record