Molecular pathways involved in the neurotoxicity of 6-OHDA, dopamine and MPTP: contribution to the apoptotic theory in Parkinson's disease

@article{Blum2001MolecularPI,
  title={Molecular pathways involved in the neurotoxicity of 6-OHDA, dopamine and MPTP: contribution to the apoptotic theory in Parkinson's disease},
  author={David Blum and Sakina Torch and Nathalie Lambeng and Marie France Nissou and Alim Louis Benabid and Rémy Sadoul and J. M. Verna},
  journal={Progress in Neurobiology},
  year={2001},
  volume={65},
  pages={135-172}
}
Neuroprotective Strategies in Parkinson’s Disease
TLDR
In spite of the extensive studies performed on postmortem substantia nigra from Parkinson’s disease patients, these studies have demonstrated that, at the time of death, a cascade of events had been initiated that may contribute to the demise of the melanin-containing nigro-striatal dopamine neurons.
Neuropharmacological approach against MPTP (1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine)-induced mouse model of Parkinson's disease.
TLDR
The neuroprotective effects of various compounds against neuronal cell loss in an MPTP model of PD may lead to a much better understanding of PD as well as provide novel clues to new targets for therapeutic interventions in PD patients.
Effects of Rotenone and 6-OHDA on Dopaminergic Neurons of the Substantia Nigra Studied In Vitro
TLDR
The neurotoxic effects of rotenone and 6-hyroxydopamine, two compounds which have been implicated in Parkinson’s disease, were investigated and it was concluded that KATP channel activation was due to oxidative stress.
Involvement of the mitochondrial apoptotic pathway and nitric oxide synthase in dopaminergic neuronal death induced by 6-hydroxydopamine and lipopolysaccharide
TLDR
The results obtained suggest that NO contributes to mitochondria-mediated neuronal apoptosis in the dopaminergic neurodegeneration induced by 6-OHDA and LPS in rats.
Parkinson's disease and a dopamine-derived neurotoxin, 3,4-Dihydroxyphenylacetaldehyde : implications for proteins, microglia, and neurons
TLDR
DOPALmediated aggregation of α-synuclein, the primary component of PD-hallmark Lewy bodies, has been suggested but was further explored in this work, which shows electrophiles and endogenous neurotoxins to play a role in this microglial activation.
Reactive oxygen and nitrogen species: weapons of neuronal destruction in models of Parkinson's disease.
TLDR
These four neurotoxins, although distinct in their intimate cytotoxic mechanisms, kill dopaminergic neurons via a cascade of deleterious events that consistently involves oxidative stress, and the emphasis is placed on how reactive oxygen and nitrogen species contribute to the neurotoxic properties of these four molecules.
6-Hydroxydopamine induces nuclear translocation of apoptosis inducing factor in nigral dopaminergic neurons in rat
TLDR
Results suggest that AIF could induce DA neuronal death by caspase-independent apoptosis in 6-OHDA treated model, although other cell death cascades should not be rule out.
Parkin protects against neurotoxicity in the 6-hydroxydopamine rat model for Parkinson's disease.
...
...

References

SHOWING 1-10 OF 485 REFERENCES
Distinct Mechanisms Underlie Neurotoxin-Mediated Cell Death in Cultured Dopaminergic Neurons
TLDR
Significant, dose-dependent levels of protection were seen in these in vitro models of PD using the C3 carboxyfullerene derivative, whereas it only partially rescued dopaminergic neurons from MPP+-induced cell death.
Some features of the nigrostriatal dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the mouse.
TLDR
It is clear that the MPTP-treated mouse is a good model for Parkinson's disease and may help to define the role of dopamine deficiency in the pathophysiology of Parkinson’s disease as well as provide a model in which potential anti-Parkinsonian therapeutic agents can be tested.
Upregulation of the anti-apoptotic protein Bcl-2 may be an early event in neurodegeneration: studies on Parkinson's and incidental Lewy body disease.
TLDR
It is proposed that Bcl-2 increases in some brain regions as an early event and that these brain regions are under a stress for perhaps many years before any symptomatic changes occur.
Cell death mechanisms in Parkinson's disease
TLDR
Findings which are in line with previous results in Alzheimer's disease and Parkinson's disease suggest that mechanisms distinct from classical apoptosis play a central role in the pathogenesis of PD and related neurodegenerative diseases.
Secondary Excitotoxicity Contributes to Dopamine-Induced Apoptosis of Dopaminergic Neuronal Cultures☆
TLDR
The results suggest for the first time that DA-induced apoptosis in dopaminergic neurons is partially attributable to increased vulnerability of these cells to non-toxic levels of excitatory amino acids, i.e., secondary excitotoxicity.
Prevention of Dopamine-Induced Cell Death by Thiol Antioxidants: Possible Implications for Treatment of Parkinson's Disease
TLDR
The data indicate that the thiol family of antioxidants, but not vitamins C and E, are highly effective in rescuing cells from DA-induced apoptosis, and study of the mechanisms underlying the unique protective capacity of thiol antioxidants may lead to the development of new neuroprotective therapeutic strategies for PD.
Participation of prostate apoptosis response‐4 in degeneration of dopaminergic neurons in models of Parkinson's disease
TLDR
It is reported that Par‐4 levels increase dramatically in midbrain dopaminergic neurons of monkeys and mice exposed to 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP), and the data suggest that Par-4 may be involved in the neurodegenerative process in PD.
...
...