Table 2. Bim Function in The Nerve System.

Apoptotic Stimulus	Remarks	References
Sympathetic neuronal death induced by NGF deprivation	• Nerve growth factor (NGF) withdrawal induced BimEL expression and apoptosis by a mechanism dependent on c-Jun. • Bim deletion protected against neuronal apoptosis. • NGF promoted MEK/MAPK-mediated phosphorylation of BimEL at Ser109 and Thr110, thereby suppressing its activity.	[125, 311, 355]
β-Amyloid-induced neuronal apoptosis	• Cdk4 and its downstream effector B-myb are required for β-amyloid-dependent Bim induction and death in cultured neurons. • β-Amyloid activates Mst-1-mediated nuclear translocation of FoxO3 that is important for Bim imduction.	[352, 388]
Thrombin-induced apoptosis of cultured cerebral cortical neurons	• Cyclin D1, Cdk4 and Bim were shown to be involved in thrombin-induced apoptosis of cultured cerebral cortical neurons.	[383]
Ischemic neuronal cell death	• Ischemia leads to neuronal cell death mediated by Notch- and NFκB-dependent Bim upregulation. • Bim-deficient mice showed decreased parenchymal loss in the hippocampal area following neonatal hypoxia-ischemia.	[351, 447]
Parkinson's disease	• Dysfunction of mitochondrial complex I leads to degeneration of dopaminergic neurons through JNK-dependent activation of Bim.	[445]
Huntington's disease	• Overexpression of mutant Huntingtin protein leads to increased BimEL expression, and knockdown of Bim prevents apoptosis mediated by mutant Huntingtin.	[180]
p75 Neurotrophin receptor (p75NTR)	• Overexpression of p75NTR induced JNK-dependent phosphorylation of BimEL at Ser65 in primary cerebellar granule neurons, which resulted in apoptosis.	[324]