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Neuroprotection and neurorestoration as experimental therapeutics for Parkinson's disease

Francardo, Veronica LU ; Schmitz, Yvonne; Sulzer, David and Cenci, M. Angela LU (2017) In Experimental Neurology
Abstract

Disease-modifying treatments remain an unmet medical need in Parkinson's disease (PD). Such treatments can be operationally defined as interventions that slow down the clinical evolution to advanced disease milestones. A treatment may achieve this outcome by either inhibiting primary neurodegenerative events ("neuroprotection") or boosting compensatory and regenerative mechanisms in the brain ("neurorestoration"). Here we review experimental paradigms that are currently used to assess the neuroprotective and neurorestorative potential of candidate treatments in animal models of PD. We review some key molecular mediators of neuroprotection and neurorestoration in the nigrostriatal dopamine pathway that are likely to exert beneficial... (More)

Disease-modifying treatments remain an unmet medical need in Parkinson's disease (PD). Such treatments can be operationally defined as interventions that slow down the clinical evolution to advanced disease milestones. A treatment may achieve this outcome by either inhibiting primary neurodegenerative events ("neuroprotection") or boosting compensatory and regenerative mechanisms in the brain ("neurorestoration"). Here we review experimental paradigms that are currently used to assess the neuroprotective and neurorestorative potential of candidate treatments in animal models of PD. We review some key molecular mediators of neuroprotection and neurorestoration in the nigrostriatal dopamine pathway that are likely to exert beneficial effects on multiple neural systems affected in PD. We further review past and current strategies to therapeutically stimulate these mediators, and discuss the preclinical evidence that exercise training can have neuroprotective and neurorestorative effects. A future translational task will be to combine behavioral and pharmacological interventions to exploit endogenous mechanisms of neuroprotection and neurorestoration for therapeutic purposes. This type of approach is likely to provide benefit to many PD patients, despite the clinical, etiological, and genetic heterogeneity of the disease.

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organization
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Contribution to journal
publication status
epub
subject
keywords
6-Hydroxydopamine, Axon sprouting, Growth factor, MPTP, Neurotrophin, Sigma-1 receptor, Synaptic plasticity, Synuclein
in
Experimental Neurology
publisher
Academic Press
external identifiers
  • scopus:85030868994
  • wos:000416296200002
ISSN
0014-4886
DOI
10.1016/j.expneurol.2017.10.001
language
English
LU publication?
yes
id
dbdf5231-f3bb-44e3-be8f-e93b92da367a
date added to LUP
2017-10-18 09:42:06
date last changed
2018-01-16 13:23:38
@article{dbdf5231-f3bb-44e3-be8f-e93b92da367a,
  abstract     = {<p>Disease-modifying treatments remain an unmet medical need in Parkinson's disease (PD). Such treatments can be operationally defined as interventions that slow down the clinical evolution to advanced disease milestones. A treatment may achieve this outcome by either inhibiting primary neurodegenerative events ("neuroprotection") or boosting compensatory and regenerative mechanisms in the brain ("neurorestoration"). Here we review experimental paradigms that are currently used to assess the neuroprotective and neurorestorative potential of candidate treatments in animal models of PD. We review some key molecular mediators of neuroprotection and neurorestoration in the nigrostriatal dopamine pathway that are likely to exert beneficial effects on multiple neural systems affected in PD. We further review past and current strategies to therapeutically stimulate these mediators, and discuss the preclinical evidence that exercise training can have neuroprotective and neurorestorative effects. A future translational task will be to combine behavioral and pharmacological interventions to exploit endogenous mechanisms of neuroprotection and neurorestoration for therapeutic purposes. This type of approach is likely to provide benefit to many PD patients, despite the clinical, etiological, and genetic heterogeneity of the disease.</p>},
  author       = {Francardo, Veronica and Schmitz, Yvonne and Sulzer, David and Cenci, M. Angela},
  issn         = {0014-4886},
  keyword      = {6-Hydroxydopamine,Axon sprouting,Growth factor,MPTP,Neurotrophin,Sigma-1 receptor,Synaptic plasticity,Synuclein},
  language     = {eng},
  month        = {10},
  publisher    = {Academic Press},
  series       = {Experimental Neurology},
  title        = {Neuroprotection and neurorestoration as experimental therapeutics for Parkinson's disease},
  url          = {http://dx.doi.org/10.1016/j.expneurol.2017.10.001},
  year         = {2017},
}