Effects of a verbenachalcone derivative on neurite outgrowth, inhibition of caspase induction and gene expression.
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.
Yeh
Li-An
LA
Laboratory for Drug Discovery in Neurodegeneration, Harvard Center for Neurodegeneration and Repair, Brigham & Women's Hospital and Harvard Medical School, 65 Landsdowne Street, Cambridge, MA 02139, USA.
Padmanaban
Deppa
D
Ho
Pei
P
Xing
Xeuchao
X
Rowley
Patricia
P
Morse
Lee Jae
LJ
Jensen
Roderick V
RV
Cuny
Gregory D
GD
D000818:Animals; D061945:Caspase Inhibitors; D020169:Caspases / Q000235:genetics; D002460:Cell Line; D002599:Chalcone / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D047188:Chalcones; D004357:Drug Synergism; D004790:Enzyme Induction / Q000187:drug effects; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D020932:Nerve Growth Factor / Q000494:pharmacology*; D016501:Neurites / Q000187:drug effects*; D016716:PC12 Cells; D051381:Rats; D013329:Structure-Activity Relationship
D061945:Caspase Inhibitors; D047188:Chalcones; C433608:verbenachalcone; D002599:Chalcone; D020932:Nerve Growth Factor; D020169:Caspases