Several lines of evidence suggest that the mechanism underlying drug-induced 
neuronal apoptosis is initiated by the increased production of reactive oxygen 
species (ROS). 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a 
neurotoxin, has been shown to initiate an apoptotic cascade by increasing ROS in 
the dopaminergic neurons of the substantia nigra, leading to the morphological 
and physiological features associated with Parkinson's disease. Recently, it has 
been reported that autophagy, a type of programmed cell death independent of the 
apoptotic cascade, also plays a role in neuronal damage. Although autophagy is 
negatively regulated by the mammalian target of rapamycin receptor (mTOR), there 
is some evidence showing a novel function for the anti-apoptotic protein Bcl-2. 
Bcl-2 is proposed to play a role in negatively regulating autophagy by blocking 
an essential protein in the signaling pathway, Beclin 1. Nevertheless, it is 
unclear whether autophagy is also correlated with apoptotic signaling in 
1-methyl-4-phenylpyridinium (MPP(+)) toxicity. Therefore, we hypothesized that 
the MPP(+) toxicity generally associated with initiating the apoptotic signaling 
cascade also increases an autophagic phenotype in neuronal cells. Using the 
SK-N-SH dopaminergic cell lines, we demonstrate that MPP(+) increases the 
expression of microtubule-associated protein light chain 3 (LC3-II), an 
autophagosome membrane marker and the mTOR signaling pathway, and Beclin 1 while 
decreasing the Bcl-2 levels. Moreover, these expressions correlate with a 
decreased binding ratio between Bcl-2 and Beclin 1, in effect limiting the 
regulation of the downstream autophagic markers, such as LC3-II. Our results 
indicate that MPP(+) can induce autophagy in SK-N-SH cells by decreasing the 
Bcl-2/Beclin 1 complex.