Neurological diseases: Targeting programmed cell death in neurodegenerative diseases

@article{Vila2003NeurologicalDT,
  title={Neurological diseases: Targeting programmed cell death in neurodegenerative diseases},
  author={Miquel Vila and Serge Przedborski},
  journal={Nature Reviews Neuroscience},
  year={2003},
  volume={4},
  pages={365-375}
}
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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529 Citations

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...

References

SHOWING 1-10 OF 190 REFERENCES

Apoptosis and autophagy in nigral neurons of patients with Parkinson's disease.

Ulastructural examination revealed characteristics of apoptosis and autophagic degeneration in melanized neurons of the substantia nigra in PD patients, suggesting that even at the final stage of the disease, the dopaminergic neurons are undergoing active process of cell death.

Histochemical detection of apoptosis in Parkinson's disease

Evidence for apoptotic cell death in Huntington disease and excitotoxic animal models

The results suggest that apoptosis occurs in both HD and excitotoxic animal models and that apoptotic and necrotic mechanisms of neuronal death may occur simultaneously within individual dying cells in the excitOToxically injured brain.

Inflammation in Neurodegenerative Disease—A Double-Edged Sword

Motoneuron Death Triggered by a Specific Pathway Downstream of Fas Potentiation by ALS-Linked SOD1 Mutations

Programmed Cell Death in Cerebral Ischemia

  • S. GrahamJun Chen
  • Biology
    Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
  • 2001
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.

Apoptosis is induced by beta-amyloid in cultured central nervous system neurons.

It is reported that synthetic A beta Ps trigger the degeneration of cultured neurons through activation of an apoptotic pathway, suggesting that apoptosis may play a role in the neuronal loss associated with Alzheimer disease.

Inhibition of caspase-1 slows disease progression in a mouse model of Huntington's disease

Evidence of caspase-1 activation in the brains of mice and humans with Huntington's disease is demonstrated and it is demonstrated that intracerebroventricular administration of a casp enzyme inhibitor delays disease progression and mortality in the mouse model of Huntington’s disease.

Huntingtin's Neuroprotective Activity Occurs via Inhibition of Procaspase-9 Processing*

It is reported that Htt overexpression in other CNS-derived cells can protect them from more than 20 days exposure to fatal stimuli and indicates that wild-type Htt (wtHtt) acts downstream of cytochrome c release.

A novel in vivo post‐translational modification of p53 by PARP‐1 in MPTP‐induced parkinsonism

It is found that p53 is heavily poly(ADP‐ribosyl)ated by PARP‐1 following MPTP intoxication, which may underlie the mechanisms of MPTP‐induced parkinsonism and other models of neuronal death.
...