The novel squamosamide derivative (compound FLZ) attenuated 1-methyl, 4-phenyl-pyridinium ion (MPP+)-induced apoptosis and alternations of related signal transduction in SH-SY5Y cells

Compound FLZ (cFLZ) is a synthetic novel derivative of natural squamosamide. Previous pharmacological study found that cFLZ improved the abnormal behavior and the decrease of dopamine content in striatunt in 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyri dine (MPTP) model mice. 1-Methyl 4-phenylpyridinium (MPP+) is the active metabolite of MPTP to cause Parkinsonism in experimental animals. The purpose of this paper was to further study the protective action of cFLZ against MPP+-induced apoptosis and alternations of related signaling transduction. The results indicated that cFLZ at concentrations of 0.1 mu M and 1 mu M prevented 100 M MPP+-induced apoptosis of SH-SY5Y cells, and inhibited the release of cytochrome C and apoptosis-inducing factor (AIF), and the activation of caspase 3 and NF-kappa B as well as alpha-synuclein gene and protein expressions. The results suggest that cFLZ possesses potent neuroprotective activity and may be a potential anti-Parkinson's disease drug worthy for further study. (c) 2006 Elsevier Ltd. All rights reserved.