Publication: Neuroprotective effects and mechanism of cognitive-enhancing choline analogs JWB 1-84-1 and JAY 2-22-33 in neuronal culture and Caenorhabditis elegans
1
0
Issued Date
2010
Resource Type
File Type
application/pdf
ISSN
17501326
Other identifier(s)
2-s2.0-78650102379
Rights Holder(s)
มหาวิทยาลัยศรีนครินทรวิโรฒ
Bibliographic Citation
Molecular Neurodegeneration. Vol 5, No.1 (2010)
Suggested Citation
Keowkase R., Aboukhatwa M., Adam B.-L., Beach J.W., Terry Jr. A.V., Buccafussco J.J., Luo Y. Neuroprotective effects and mechanism of cognitive-enhancing choline analogs JWB 1-84-1 and JAY 2-22-33 in neuronal culture and Caenorhabditis elegans. Molecular Neurodegeneration. Vol 5, No.1 (2010). doi:10.1186/1750-1326-5-59 Retrieved from: https://hdl.handle.net/20.500.14740/7436
Abstract
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 -amyloid (A) levels and found that both compounds significantly reduced A levels. JWB1-84-1 and JAY2-22-33 also protected rat primary cortical neurons from A 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 A toxicity, human A is expressed intracellularly in the body wall muscle. The expression and subsequent aggregation of A in the muscle leads to progressive paralysis. Conclusion. We found that JAY2-22-33 (but not JWB1-84-1) significantly reduced A toxicity by delaying paralysis and this protective effect required both the insulin signaling pathway and nicotinic acetylcholine receptors (nAChRs). © 2010 Keowkase et al; licensee BioMed Central Ltd.
Subject(s)
Amyloid beta protein
Amyloid precursor protein
Choline derivative
Jay 2 22 33
Jwb 1 84 1
Nicotine derivative
Presenilin 1
Unclassified drug
Alzheimer disease
Animal experiment
Animal model
Article
Brain cell
Caenorhabditis elegans
Cell culture
Cognition
Controlled study
Drug effect
Drug structure
Drug targeting
Gene mutation
Human
Human cell
In vitro study
In vivo study
Neuroprotection
Nonhuman
Protein blood level
Protein expression
Rat
Caenorhabditis elegans
Mus musculus
Rattus
Amyloid precursor protein
Choline derivative
Jay 2 22 33
Jwb 1 84 1
Nicotine derivative
Presenilin 1
Unclassified drug
Alzheimer disease
Animal experiment
Animal model
Article
Brain cell
Caenorhabditis elegans
Cell culture
Cognition
Controlled study
Drug effect
Drug structure
Drug targeting
Gene mutation
Human
Human cell
In vitro study
In vivo study
Neuroprotection
Nonhuman
Protein blood level
Protein expression
Rat
Caenorhabditis elegans
Mus musculus
Rattus