Neuronal death apoptosis

There is an increasing body of evidence that supports an apoptosis-necrosis cell death continuum. In this continuum, neuronal death can result from varying contributions of coexisting apoptotic and necrotic mechanisms [2]. Therefore the distinct designations... 

Mechanisms of Neuronal Death in Neurodegenerative Disorders General Concepts 347 Apoptosis 348... 

Greenlund, L. J., Deckwerth, T. L. and Johnson, E. M. Jr. Superoxide dismutase delays neuronal apoptosis a role for reactive oxygen species in programmed neuronal death. Neuron 14 303-315,1995. 

Martin, L. J. Neuronal death in amyotrophic lateral sclerosis is apoptosis possible contribution of a programmed cell death mechanism. /. Neuropathol. Exp. Neurol. 58 459-471, 1999. 

In order to test whether water-soluble fullerenes could be potential agents against the treatment of Parkinson s disease and other CNS degenerative diseases related to neuronal apoptosis, the protective effects of water-soluble fullerene derivatives 1 and 6-8 on 6-hydroxydopamine-induced apoptosis of CNS dopaminergic neurons (Silva et al., 2005) in developing zebrafish were investigated. It was demonstrated that 1,6 and 7 were able to protect 42%, 47% and 23%, respectively of total CNS neurons, whereas 1,6 and 8 blocked each with 60%, 100% and 60% of specific dopaminergic neuronal death in the diencephalon as it is exemplarily shown for 8 in Fig. 3.8. 

A recent report suggests that inhibition of PC synthesis constitutes one of the primary events by which C2-ceramide triggers apoptosis (Ramos et al, 2000). Treatment of cerebral granule neurons with C2-ceramide resulted in a rapid (within 1 hour) reduction in PC biosynthesis, whereas only 6 h after exposure to the agonists the first significant drop in cell viability was observed. The authors further showed that addition of exogenous PC resulted in a dose-dependent full prevention of neuronal death. This was specific for PC, because addition of other glycerohpids Uke, PE, PS, phosphatidylinositol and phosphatidic acid had no effect on C2-ceramide-induced apoptosis. 

Figure I. Chromatin acetylation status, transcription and survival a balance between HAT and HDAC activities, (a) Transcriptional activationlrepression relies on the chromatin acetylation status of histones. TBP TATA-Binding Protein, TF Transcription Factor, TR Transcriptional Repressor, (b) A fine-tuning of HAT/HDAC activities orchestrates neuronal death and survival. On one hand, acetylation levels can be decreased (HypoAc) because of CBP loss of function, as observed during apoptosis and neurodegeneration. On the other hand, when the threshold of acetylation is exceeded (HyperAc), this ultimately leads to nemonal death. (See Colom Plate 16.)...

Neuronal cell death is required for the development of the nervous system. However, recent studies suggest that neurons die from programmed cell death (apoptosis) in brains deprived of oxygen by stroke [14] and trauma [15], and in the brains of Alzheimer s patients [16], Therefore, prevention of neuronal apoptosis has been considered to be a desirable therapeutic strategy for treating such neurodegenerative diseases, although the value of this approach is not yet evident. We have recently reported that crocin suppresses tumor necrosis factor (TNF)-a-... 

What are the possible adverse consequences of accumulation of the A(3 protein It may cause inflammation by activation of microglia,1157 which may cause damage by release of NO.1206 A(3 may induce death of neurons by apoptosis.1201 1207-1209 A defect in protesomal degradation may be a factor.1208 Both Ap and the prion protein may promote oxidative damage. The brain derives most of its energy from oxidative metabolism, a major source of damaging radicals. Mitochondria are found in dendrites as well as cell bodies.1210 Methionine residues in glycine-rich parts of the AP and prion proteins are suspected as centers of free radical formation.1202 1211... 

FIGURE 1 — 18. Neuronal death can occur by either necrosis or apoptosis. Necrosis is analogous to neuronal assassination, in which neurons explode and cause an inflammatory reaction after being destroyed by poisons, suffocation, or toxins such as glutamate. On the other hand, apoptosis is akin to neuronal suicide and results when the genetic machinery is activated to cause the neuron to literally fade away without causing the molecular mess of necrosis. 

Stahl, S.M. (1997) Apoptosis neuronal death by design. Journal of Clinical Psychiatry 58(5), 183-5. 

The identity of factors released from damaged neurons to signal microglial cell activation may depend upon which type of neural cell is damaged, neuron versus glial, and on the the toxin or stimulus, glutamate versus /1-amyloid versus a-synuclein, and the nature of cellular death, apoptosis versus necrosis. Similarly, the molecular mechanisms and internal and external factors that modulate the dynamic aspects of acute and chronic inflammation in cell injury mediated by glutamate remain unclear. It also remains unclear to what extent inflammation is beneficial... 

Interplay among excitotoxicity, oxidative stress, and neuroinflammation facilitates neuronal death via apoptosis as well as necrosis (Nicotera and Lipton, 1999 Sastry and Rao, 2000 Farooqui et al., 2004). In neurons, intracellular energy levels and mitochondrial function are rapidly compromised in necrosis, but not in apoptosis, suggesting that the ATP level is a prominent factor in determining the neurochemical events associated with apoptotic and necrotic neural cell death (Nicotera and Leist, 1997 Liu et al., 2001). Apoptosis and necrosis represent the extreme ends of the spectrum of mechanisms for neural cell death (Williamson and Schlegel, 2002 Leist and Nicotera, 1998 Nicotera and Lipton, 1999). 

Ankarcrona, M., Dypbukt, J. M., Bonfoco, E., Zhivotovsky, B., Orrenius, S., Lipton, S. A., and Nicotera, P., 1995, Glutamate-induced neuronal death a succession of necrosis or apoptosis depending on... 

Activation of calpain is usually associated with the progression of a necrotic type of cell death (Wang, 2000). However, neuronal necrosis and apoptosis occur in parallel after ischemic injury in vitro and in vivo (Charriaut-Marlangue et al., 1996). Retinal ischemia causes precocious necrosis of neurons in the ganglion cell layer (GCL) and INL, whereas apoptosis appears as the delayed component of neuronal death associated with transient retinal ischemia (Joo et al., 1999). 

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