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…
525 Citations
Cell Death and Neurodegeneration.
- BiologyCold Spring Harbor perspectives in biology
- 2019
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.
- Biology, ChemistryParkinsonism & related disorders
- 2008
Cell Death Mechanisms of Neurodegeneration.
- BiologyAdvances in neurobiology
- 2017
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.
Apoptotic cascades as possible targets for inhibiting cell death in Huntington’s disease
- BiologyJournal of Neurology
- 2006
Minocycline, a tetracycline-derived antibiotic that has been shown to increase survival in transgenic mouse models of HD, exhibits a neuroprotective feature in HD and demonstrates anAnti-inflammatory as well as an anti-microbial effect by inhibiting microglial activation known to cause apoptosis.
Parkinson's disease: molecular aspects and prospective neuroprotective and restorative therapies
- Biology, Psychology
- 2006
This review summarizes most recent insights gained from many studies in Parkinson's disease and identifies the cascade of deleterious events that lead to the dysfunction and death of dopaminergic neurons.
What causes cell death in Parkinson's disease?
- BiologyAnnals of neurology
- 2008
Many of the advances in the last decade regarding the identification of new targets for the treatment of PD based on understanding the molecular mechanisms of how mutations in genes linked to PD cause neurodegeneration are reviewed.
The Antiapoptotic Activity of Melatonin in Neurodegenerative Diseases
- BiologyCNS neuroscience & therapeutics
- 2009
This review summarizes the reports to date showing inhibition by melatonin of the intrinsic apoptotic pathways in neurodegenerative diseases including stroke, Alzheimer disease, Parkinson disease, Huntington disease, and amyotrophic lateral sclerosis.
Molecular targets for neuroprotection
- Biology, PsychologyAmyotrophic lateral sclerosis and other motor neuron disorders : official publication of the World Federation of Neurology, Research Group on Motor Neuron Diseases
- 2004
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.
Fighting neurodegeneration with rapamycin: mechanistic insights
- Biology, ChemistryNature Reviews Neuroscience
- 2011
The molecular mechanisms underlying the neuroprotective effects of rapamycin are reviewed and the therapeutic potential of this compound for neurodegenerative diseases is discussed.
References
SHOWING 1-10 OF 190 REFERENCES
Apoptosis and autophagy in nigral neurons of patients with Parkinson's disease.
- BiologyHistology and histopathology
- 1997
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
- Biology, MedicineJournal of the Neurological Sciences
- 1996
Evidence for apoptotic cell death in Huntington disease and excitotoxic animal models
- BiologyThe Journal of neuroscience : the official journal of the Society for Neuroscience
- 1995
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.
Motoneuron Death Triggered by a Specific Pathway Downstream of Fas Potentiation by ALS-Linked SOD1 Mutations
- BiologyNeuron
- 2002
Programmed Cell Death in Cerebral Ischemia
- BiologyJournal 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.
- BiologyProceedings of the National Academy of Sciences of the United States of America
- 1993
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.
p53 inhibitors preserve dopamine neurons and motor function in experimental parkinsonism
- BiologyAnnals of neurology
- 2002
It is reported that two novel synthetic inhibitors of the tumor suppressor protein p53, pifithrin‐α (PFT‐α) and Z‐1‐117, are highly effective in protecting midbrain dopaminergic neurons and improving behavioral outcome in a mouse model of Parkinson's disease.
Inhibition of caspase-1 slows disease progression in a mouse model of Huntington's disease
- Biology, MedicineNature
- 1999
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.
Neuronal death in amyotrophic lateral sclerosis is apoptosis: possible contribution of a programmed cell death mechanism.
- BiologyJournal of neuropathology and experimental neurology
- 1999
It is concluded that a PCD mechanism, involving cytosol-to-membrane and membrane- to-cytosol redistribution of cell death proteins and caspase-3 activation, participates in the pathogenesis of ALS.
A Drosophila model of Parkinson's disease
- Biology, PsychologyNature
- 2000
The Drosophila model recapitulates the essential features of the human disorder, and makes possible a powerful genetic approach to Parkinson's disease.