Functional models of Parkinson's disease: A valuable tool in the development of novel therapies

@article{Jenner2008FunctionalMO,
  title={Functional models of Parkinson's disease: A valuable tool in the development of novel therapies},
  author={Peter Jenner},
  journal={Annals of Neurology},
  year={2008},
  volume={64}
}
  • P. Jenner
  • Published 2008
  • Medicine
  • Annals of Neurology
Functional models of Parkinson's disease (PD) have led to effective treatment for the motor symptoms. Toxin‐based models, such as the 6‐hydroxydopamine–lesioned rat and 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine–treated primate, have resulted in novel dopaminergic therapies and new therapeutic strategies. They have also been used to study processes underlying motor complications, particularly dyskinesia, and for developing pharmacological approaches to dyskinesia avoidance and suppression… Expand
Animal models of Parkinson's disease: a source of novel treatments and clues to the cause of the disease
TLDR
The MPTP‐treated primate model of PD, which closely mimics the clinical features of PD and in which all currently used anti‐parkinsonian medications have been shown to be effective, is undoubtedly the most clinically‐relevant of all available models. Expand
Animal models of the non-motor features of Parkinson's disease
TLDR
This review summarizes the current available literature on the ability of both toxin-induced and genetically-based animal models to reproduce the non-motor symptoms of Parkinson's disease. Expand
Neuroprotective Surgical Strategies in Parkinson’s Disease: Role of Preclinical Data
TLDR
It is argued that NSI are promising approaches for neurorestoration in PD, but preclinical studies should be planned carefully in order not only to detect benefits but also to detect potential adverse effects, and clinical trials should be designed to be able to detect and disentangle neuroprotection from symptomatic effects. Expand
Comprehensive Perspectives on Experimental Models for Parkinson’s Disease
TLDR
This review systemically summarized experimental PD models, including cellular and animal models used in preclinical studies, to understand the pathogenesis of PD. Expand
Possible Anti-Parkinson’s Disease Therapeutics From Nature: A Review
TLDR
A review of the literature covering use of botanical-derived natural products, either as crude extracts or isolated compounds in monoherbal or polyherbal formulations, having anti-PD activity with notes on source plant, active component, experimental methodology, and ethnopharmacological relevance of anti- PD efficacy of the natural compounds. Expand
Non-human primate models of PD to test novel therapies
TLDR
Non-human primate models of Parkinson disease show many similarities with the human disease and have been useful to seek new drug targets, since they reproduce motor complications observed in parkinsonian patients as reviewed here. Expand
A behavioural evaluation of the potential of nNOS inhibitors to control dyskinesia in animal models of Parkinson's disease
TLDR
In conclusion, inhibition of nNOS in 6-OHDA-lesioned rats and MPTP-treated primates did not reduce the expression or priming of L-dopaor ropinirole-induced dyskinesia and it is suggested that nN OS inhibitors would not be beneficial in either preventing or attenuating motor complications in PD patients. Expand
Parkinson's disease: Unresolved issues
TLDR
The therapeutic story of PD has been one of clinical success based on scientifically derived solutions, and has resulted in better treatments and better outcomes for millions of patients around the world, and this supplement will consider some of these unresolved issues. Expand
Behavioral phenotyping of mouse models of Parkinson's disease
TLDR
An extensive, yet feasible, battery of behavioral tests for mouse models of PD aimed to better assess both non-motor and motor deficits associated with the disease are suggested. Expand
Genetic Models of Parkinson’s Disease
TLDR
The design of such Tamoxifen inducible transgene constructs and the use of premade conditional knockout alleles generated by large-scale mutagenesis projects are covered and an overview of the available brain-specific CreER(T2) mouse lines is provided. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 258 REFERENCES
An update on the treatment of Parkinson's disease.
  • J. Jankovic
  • Medicine
  • The Mount Sinai journal of medicine, New York
  • 2006
TLDR
Future therapeutic strategies should focus not only on ameliorating the symptoms of PD, but also on neuroprotective or neurorescue therapies that can favorably modify the natural course of the disease and slow the progression of both motor and nonmotor manifestations of PD. Expand
The need for neuroprotective therapies in Parkinson’s disease
TLDR
Current evidence suggests that it may soon be possible to define populations at increased risk to develop PD and thus to target the “preclinical” phase of PD for neuroprotection, and future trials will test intervention for their ability to prevent or retard the development of clinically overt PD in at-risk individuals. Expand
Viral Vector Mediated Overexpression of Human α-Synuclein in the Nigrostriatal Dopaminergic Neurons: A New Model for Parkinson's Disease
TLDR
Recent findings relating a-synuclein with Parkinson's disease pathology have opened new possibilities to develop alternative models based on the overexpression of this protein using recombinant adeno-associated viral vectors, which are valuable not only for helping to better understand its involvement in the disease process, but also to more closely resemble the neurodegeneration found in Parkinson’s disease. Expand
Rasagiline in the pharmacotherapy of Parkinson’s disease – a review
  • O. Rascol
  • Medicine
  • Expert opinion on pharmacotherapy
  • 2005
TLDR
Rasagiline is a monoamine oxidase-B inhibitor that has demonstrated efficacy against the cardinal symptoms of Parkinson's disease when used as monotherapy in early Parkinson’s disease, and as an adjunct to levodopa in advanced disease stages. Expand
Systemic exposure to proteasome inhibitors causes a progressive model of Parkinson's disease
TLDR
This animal model induced by proteasome inhibitors closely recapitulates key features of PD and may be valuable in studying etiopathogenic mechanisms and putative neuroprotective therapies for the illness. Expand
Recent clinical failures in Parkinson's disease with apoptosis inhibitors underline the need for a paradigm shift in drug discovery for neurodegenerative diseases.
TLDR
Two recent clinical failures require a reassessment of both the relevance of apoptosis to neurodegenerative disease etiology and the available animal models used to prioritize NCEs for advancement to the clinic in this area. Expand
Preclinical evidence for neuroprotection with monoamine oxidase-B inhibitors in Parkinson’s disease
TLDR
It is apparent that stopping the progression of pathology that leads to the onset of PD is key to preventing the appearance and development of motor impairment. Expand
Levodopa in the treatment of Parkinson's disease: Current controversies
  • C. Olanow, Y. Agid, +25 authors F. Stocchi
  • Psychology, Medicine
  • Movement disorders : official journal of the Movement Disorder Society
  • 2004
TLDR
Treatment strategies that provide more continuous stimulation of dopamine receptors provide reduced motor complications in MPTP monkeys and PD patients and studies raise the possibility that more continuous and physiological delivery of levodopa might reduce the risk of motor complications. Expand
3,4-Dihydroxyphenylalanine Reverses the Motor Deficits in Pitx3-Deficient Aphakia Mice: Behavioral Characterization of a Novel Genetic Model of Parkinson's Disease
TLDR
It is demonstrated that Pitx3-deficient aphakia (ak) mice, which have been shown previously to exhibit a major loss of substantia nigra dopaminergic neurons, display motor deficits that are reversed by l-DOPA and evidence of “dopaminergic supersensitivity” in the striatum. Expand
Advances in the Pharmacologic Management of Early Parkinson Disease
TLDR
Treatment of early PD with an MAO-B inhibitor, dopamine agonist, or amantadine, may provide useful alternatives to treatment with levodopa and preclinical studies suggest that adjunctive use of the catechol-O-methyltransferase (COMT) inhibitor entacapone whenlevodopa is first introduced may be associated with fewer motor complications than treatment with Levodopa alone. Expand
...
1
2
3
4
5
...