Brain chemotherapy from the bench to the clinic: targeting neuronal survival with small molecule inhibitors of apoptosis.
Increasing evidence implicates aberrant apoptosis as a fundamental cause of neurodegenerative diseases. Thus elucidating the underlying causes of neuronal programmed cell death may foster the development of therapeutic interventions. Research in the last 15 years provided a solid foundation for understanding molecular mechanisms of neuronal apoptosis. This review discusses the major molecules and signaling pathways leading to neuronal survival or apoptosis with emphasis on several small molecule inhibitors that target neuronal survival with the hope of impeding the detrimental effects of neurodegenerative diseases.
Chin
Paul C
PC
The Molecular and Cell Biology Department, FO 3.1, The University of Texas at Dallas, P.O. Box 830688, Richardson, Texas 75083-0688, USA.
D'Mello
Santosh R
SR
D000818:Animals; D017209:Apoptosis; D001932:Brain Neoplasms / Q000188:drug therapy*; D002227:Carbazoles / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D008954:Models, Biological; D019636:Neurodegenerative Diseases / Q000473:pathology; D009474:Neurons / Q000378:metabolism*; D010636:Phenols / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D002227:Carbazoles; D004791:Enzyme Inhibitors; D007211:Indoles; D048670:MAP Kinase Kinase 4; D010636:Phenols; D019869:Phosphatidylinositol 3-Kinases; D019253:Proto-Oncogene Proteins c-bcl-2; D048051:p38 Mitogen-Activated Protein Kinases; C106592:3,9-bis((ethylthio)methyl)-K-252a; C489251:5-iodo-3-((3,5-dibromo-4-hydroxyphenyl)methylene)-2-indolinone