Effects of a verbenachalcone derivative on neurite outgrowth, inhibition of caspase induction and gene expression.

Abstract

A verbenachalcone derivative was synthesized and shown to protect N2a cells from caspase induction caused by serum starvation and to enhance the effect of NGF on neurite outgrowth in PC12 cells. As an initial investigation of the compound's mechanism(s) of action, we performed differential gene expression profiling in PC12 cells using oligonucleotide ( approximately 10,000 gene probes) microarrays. Gene expression patterns were compared in the presence of NGF (2 and 50 ng/mL) and NGF (2 ng/mL) plus the verbenachalcone derivative. Ten genes were significantly (2-fold; p0.05) up-regulated and seven genes were significantly down-regulated in the presence of the compound. These results were independently validated by quantitative real-time PCR for a subset of genes (cathepsin L, sigma-1 receptor and protein tyrosine phosphatase receptor type R). These genes or their protein products may represent useful therapeutic targets for treating neurodegeneration, such as Alzheimer's disease.

• Authors: Li-An Yeh, Deppa Padmanaban, Pei Ho, Xeuchao Xing, Patricia Rowley, Lee Jae Morse, Roderick V Jensen, Gregory D Cuny
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 15 Issue 4 Pg. 1193-6 (Feb 15 2005) ISSN: 0960-894X [Print] England
• PMID: 15686940 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Caspase Inhibitors
• Chalcones
• verbenachalcone
• Chalcone
• Nerve Growth Factor
• Caspases

Topics

• Animals
• Caspase Inhibitors
• Caspases (genetics)
• Cell Line
• Chalcone (analogs & derivatives, chemical synthesis, pharmacology)
• Chalcones
• Drug Synergism
• Enzyme Induction (drug effects)
• Gene Expression Profiling
• Gene Expression Regulation (drug effects)
• Humans
• Nerve Growth Factor (pharmacology)
• Neurites (drug effects)
• PC12 Cells
• Rats
• Structure-Activity Relationship