Neurotoxin-based models of Parkinson's disease

Bové, Jordi; Perier, Céline

doi:10.1016/j.neuroscience.2011.10.057

Cited by 445 publications

(385 citation statements)

References 327 publications

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“…The oxidation of 6-OHDA is known to produce p-quinones as well as free radicals such as hydrogen peroxides, superoxides, and hydroxyl radicals that induce apoptosis in cells. 37,38 MPP+, which is a metabolite of MPTP, is a dopaminergic neurotoxin that destroys the nigrostriatal dopaminergic pathway and produces Parkinsonian syndrome with a massive loss of nigral DA neurons. 39−41 The inhibition of mitochondrial complex I by MPP+, which increases the oxidative stress, is the central mechanism for its toxicity.…”

Section: ■ Discussionmentioning

confidence: 99%

D-512 and D-440 as Novel Multifunctional Dopamine Agonists: Characterization of Neuroprotection Properties and Evaluation of In Vivo Efficacy in a Parkinson’s Disease Animal Model

Santra

Shah

et al. 2013

ACS Chem. Neurosci.

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In this Article, we have demonstrated the in vivo efficacy of D-512 and D-440 in a 6-OHDA-induced unilaterally lesioned rat model experiment, a Parkinson's disease animal model. D-512 is a novel highly potent D2/D3 agonist, and D-440 is a novel highly selective D3 agonist. We evaluated the neuroprotective properties of D-512 and D-440 in the dopaminergic MN9D cells. Cotreatment of these two drugs with 6-OHDA and MPP+ significantly attenuated and reversed 6-OHDA-and MPP+-induced toxicity in a dosedependent manner in the dopaminergic MN9D cells. The inhibition of caspase 3/7 and lipid peroxidation activities along with the restoration of tyrosine hydroxylase levels by D-512 in 6-OHDA-treated cells may partially explain the mechanism of its neuroprotective property. Furthermore, studies were carried out to elucidate the time-dependent changes in the pERK1/2 and pAkt, two kinases implicated in cell survival and apoptosis, levels upon treatment with 6-OHDA in presence of D-512. The neuroprotective property exhibited by these drugs was independent of their dopamine-agonist activity, which is consistent with our multifunctional drug-development approach that is focused on the generation of disease-modifying symptomatic-treatment agents for Parkinson's disease.

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Section: ■ Discussionmentioning

confidence: 99%

D-512 and D-440 as Novel Multifunctional Dopamine Agonists: Characterization of Neuroprotection Properties and Evaluation of In Vivo Efficacy in a Parkinson’s Disease Animal Model

Santra

Shah

et al. 2013

ACS Chem. Neurosci.

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“…We then tested the neuroprotective properties of the X protein in vivo using the MPTP intoxication mouse model of PD 23,24 . LVs expressing either wt (LV-X wt ) or its non-mitochondrial mutant (LV-X A6A7 ) were introduced by stereotaxic injection in the substantia nigra pars compacta (SNpc), 2 weeks before MPTP intoxication.…”

Section: Bdv Protects From Rotenone-induced Axonal Fragmentationmentioning

confidence: 99%

A viral peptide that targets mitochondria protects against neuronal degeneration in models of Parkinson’s disease

et al. 2014

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Mitochondrial dysfunction is a common feature of many neurodegenerative disorders, notably Parkinson's disease. Consequently, agents that protect mitochondria have strong therapeutic potential. Here, we sought to divert the natural strategy used by Borna disease virus (BDV) to replicate in neurons without causing cell death. We show that the BDV X protein has strong axoprotective properties, thereby protecting neurons from degeneration both in tissue culture and in an animal model of Parkinson's disease, even when expressed alone outside of the viral context. We also show that intranasal administration of a cellpermeable peptide derived from the X protein is neuroprotective. We establish that both the X protein and the X-derived peptide act by buffering mitochondrial damage and inducing enhanced mitochondrial filamentation. Our results open the way to novel therapies for neurodegenerative diseases by targeting mitochondrial dynamics and thus preventing the earliest steps of neurodegenerative processes in axons.

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“…Загальновизнані механізми нейродегене-рації при ХП включають розвиток оксида-тивного стресу, нейрозапалення з активацією мікроглії, ушкодження шляхів деградації про-теїнів, глутаматергічну ексайтотоксичність, дисфункцію мітохондрій тощо, а основним шляхом загибелі нервових клітин є апоптоз [3,4]. Існує думка, що саме оксидативний стрес -один із ключових факторів ушкод-ження клітинних мембран, органел і нуклеї-нових кислот дофамінергічних нейронів та їх наступної загибелі [5].…”

Section: вступunclassified

Thymic Hormones, Antioxidant Enzymes and Neurogenesis of Bulbus Olfactorius in Rats With Parkinsonism: The Effect of Melatonin

If¹,

Sa²,

Rg³

et al. 2015

Fiziol Zh

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Neurotoxin-based models of Parkinson's disease

Cited by 445 publications

References 327 publications

D-512 and D-440 as Novel Multifunctional Dopamine Agonists: Characterization of Neuroprotection Properties and Evaluation of In Vivo Efficacy in a Parkinson’s Disease Animal Model

D-512 and D-440 as Novel Multifunctional Dopamine Agonists: Characterization of Neuroprotection Properties and Evaluation of In Vivo Efficacy in a Parkinson’s Disease Animal Model

A viral peptide that targets mitochondria protects against neuronal degeneration in models of Parkinson’s disease

Thymic Hormones, Antioxidant Enzymes and Neurogenesis of Bulbus Olfactorius in Rats With Parkinsonism: The Effect of Melatonin

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