Neurological diseases: Targeting programmed cell death in neurodegenerative diseases

  title={Neurological diseases: Targeting programmed cell death in neurodegenerative diseases},
  author={Miquel Vila and Serge Przedborski},
  journal={Nature Reviews Neuroscience},
Molecular pathways of programmed cell death (PCD) are activated in various neurodegenerative disorders including Parkinson's disease, amyotrophic lateral sclerosis and Huntington's disease. In these diseases, PCD might be pathogenic, and targeting it might mitigate neurodegeneration. To identify potential neuroprotective targets within the PCD machinery, the expression and activity of some of its components have been altered by genetic or pharmacological means in experimental models of… 

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How neuronal death may occur during disease in response to neuron intrinsic and extrinsic stressors is addressed and an improved understanding of the molecular mechanisms underlying neuronal dysfunction and cell death is addressed.

Molecular pathways of programmed cell death in experimental Parkinson's disease.

Cell Death Mechanisms of Neurodegeneration.

There are common mechanisms shared by genetically or pathologically distinct neurodegenerative diseases, such as excitotoxicity, mitochondrial deficits and oxidative stress, protein misfolding and translational dysfunction, autophagy and microglia activation, that may lead to final execution of cell death through similar pathways.

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Experimental models of ALS such as the transgenic rodents expressing mutant superoxide dimutase‐1 are playing a pivotal role in the understanding of ALS pathogenesis, and in the testing of new therapeutic interventions aimed at protecting against neurodegeneration.

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The contribution of death receptors of the tumor necrosis factor (TNF)/nerve growth factor (NGF) family to cell death and survival in the context of CNS pathology is reviewed, indicating the possible value of manipulating cell death induced by these receptors for the treatment of CNS diseases and injury.



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Histochemical detection of apoptosis in Parkinson's disease

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The most convincing evidence for the induction of PCD after ischemia includes the altered expression and activity in the ischemic brain of deduced key death-regulatory genes, and studies provide strong support for the hypothesis that PCD contributes to neuronal cell death caused by isChemic injury.

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