Neuronal death

PD affects approximately one million Americans (1% of people over 60 years of age). The average age of onset is 60 years of age, and PD is fairly uncommon in those under age 40. The etiology of PD is unknown, but genetic predisposition, environmental factors, or combinations of these have been proposed to explain why nerve cells in the substantia nigra deteriorate. About 15% of patients with PD have a first-degree relative with the disease. The pathogenesis of cell death (neuron degeneration) may be due to oxidative stress, mitochondrial... 

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. 

Yuan, Y., Lipinski, M., and Degterev, A. Diversity in the mechanisms of neuronal cell death. Neuron 40 401-413, 2003. 

Leissring, M.A., Farris, W., Chang, A.Y., Walsh, D.M., Wu, X., Sun, X., Frosch, M.P., and Selkoe, D.J., Enhanced proteolysis of beta-amyloid in APP transgenic mice prevents plaque formation, secondary pathology, and premature death, Neuron, 40,1087, 2003. 

MPTP is one example of a toxicant that causes direct structural damage to neurons, resulting in loss of function. In the following sections, other types of structural and functional effects of neurotoxicants are described. Structural effects are divided into three primary types effects on myelin formation, primary damage to axons, and direct promotion of cell death. Neurons may also be secondarily affected by neurotoxicants... 

Leissring, M.A., et al. (2003). Enhanced proteolysis of beta-amyloid in APP transgenic mice prevents plaque formation, secondary pathology, and premature death. Neuron 40 1087-1093. 

Pettmann B, Henderson CP (1998) Neuronal cell death. Neuron 20 633-647. 

Forrest D, Yuzaki M, Soares HD, Ng L, Luk DC, Sheng M, Stewart CL, Morgan JI, Connor JA, Curran T (1994) Targeted disruption of NMDA receptor 1 gene abolishes NMDA response and results in neonatal death. Neuron 73 325-338. 

Fig. 1. Schematic diagram outlining the neurotrophic theory of cell death. Neurons extend axons in the presence of a low circulating level of neurotrophic factors. At a critical point in their development, usually corresponding to the period of target tissue innervation, the neuron becomes acutely dependent on the neurotrophic factor for its survival. At this stage those that make appropriate connections in the periphery obtain sufficient factor for their survival. Those not making correct connections do not obtain sufficient factor and die.

C. Haass, Presenilins genes for life and death . Neuron 1997,18, 687-690. 

As of the mid-1990s, use of MAOIs for the treatment of depression is severely restricted because of potential side effects, the most serious of which is hypertensive crisis, which results primarily from the presence of dietary tyramine. Tyramine, a naturally occurring amine present in cheese, beer, wine, and other foods, is an indirecdy acting sympathomimetic, that is, it potently causes the release of norepinephrine from sympathetic neurons. The norepinephrine that is released interacts with adrenoceptors and, by interacting with a-adrenoceptors, causes a marked increase in blood pressure the resultant hypertension may be so severe as to cause death. 

The nervous system is vulnerable to attack from several directions. Neurons do not divide, and, therefore, death of a neuron always causes a permanent loss of a cell. The brain has a high demand for oxy gen. Lack of oxygen (hypoxia) rapidly causes brain damage. This manifests itself both on neurons and oligodendroglial cells. Anoxic brain damage may result from acute carbon monoxide, cyanide, and hydrogen sulfide poisonings. Carbon monoxide may also be formed in situ in the metabolism of dichloromethylene. 

While advances in the symptomatic drug therapy (summarized below) have certainly improved the lives of many Parkinson patients, the goal of current research is to develop treatments that can prevent, retard or reverse the death of dopaminergic neurons in the substantia nigra pats compacta (and of other neurons involved in the pathogenesis of Parkinson s disease not mentioned in this essay). 

Degeneration and death of dopamine neurons, resulting from neurotoxic agent. 

Excitotoxicity is the over-activity of the glutamatergic system responsible for the large number of dead neurons observed after ischemia (stroke) or epileptic seizures. This neuronal death is due to an overexcitation of the neurons and the massive Ca2+ entry... 

Kir3.2 Weaver mouse. A mutant mouse with cer ebellar degeneration and motor dysfunction resulting from a serine for glycine substitution in the -GYG- sequence of the K selectivity filter of Kir3.2. G-protein activated K conductances are abolished in the cerebellar neurons, leading to Ca2+ overload and cell death. 

An episode of acute regional ischemia in the brain leading to neuronal death. It is usually caused by thrombi or emboli from atherosclerotic plaques. 

Neuronal cell deterioration Neuronal cell death... 

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... 

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