Apoptosis and the Nervous System


  • Abbreviations used: BDNF, brain-derived neurotrophic factor; CDF, cholinergic differentiation factor; CNTF, ciliary neurotrophic factor; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; IAP, inhibitor of apoptosis; ICE, interleukin-1β converting enzyme; IRP, ICE-related protease; JNK, c-Jun N-terminal kinase; MDMA, 3,4-methylenedioxymethamphetamine; MPP+, 1-methyl-4-phenylpyridinium; MPTP, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; NGF, nerve growth factor; NMDA, N-methyl-D-aspartate; NO, nitric oxide; NT, neurotrophin; PCD, programmed cell death; ROS, reactive oxygen species; SOD, superoxide dismutase; TUNEL, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling; Z-D-DCB, benzyloxycarbonyl-Asp-CH2OC(O)-2,6-dichlorobenzene; ZVAD-fmk, benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone.

Address correspondence and reprint requests to Prof. K. S. Rao at Department of Biochemistry, University of Hyderabad, Hyderabad 500046, India. E-mail: ksrsl@uohyd.ernet.in


Abstract: Apoptosis is now recognized as a normal feature in the development of the nervous system and may also play a role in neurodegenerative diseases and aging. This phenomenon has been investigated intensively during the last 6-7 years, and the progress made in this field is reviewed here. Besides a few in vivo studies, a variety of neuronal preparations from various parts of the brain, the majority of which were primary cultures, and some cell lines have been investigated. Several apoptosis-inducing agents have been identified, and these include lack of neurotrophic support, neurotransmitters, neurotoxicants, modulators of protein phosphorylation and calcium homeostasis, DNA-damaging agents, oxidative stress, nitric oxide, and ceramides. The precise signaling cascade is not well established, and there are lacunae in many suggested pathways. However, it appears certain that the Bcl family of proteins is involved in the apoptotic pathway, and these proteins in turn affect the processing of interleukin-1β converting enzyme (ICE)/caspases. The available evidence suggests that there may be several apoptotic pathways that may depend on the cell type and the inducing agent, and most of the pathways may converge at the ICE/caspases step.