Dopamine D3 receptor agonists for protection and repair in Parkinson's disease

Joyce, Jeffrey N.; Millan, Mark J.

doi:10.1016/j.coph.2006.11.004

Cited by 102 publications

(73 citation statements)

References 46 publications

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“…* P \ 0.05, ** P \ 0.01 versus control and # P \ 0.05, ## P \ 0.01 vs lactacystin caused nigral DA neuron degeneration is consistent with other reports [21,22]. Using this animal model we demonstrated that PPX has neuroprotective effect presumably through the enhancement of UPS impairment recovery, and the increase of BDNF and GDNF expression, and the inhibition of microglial activation in the nigro-striatal pathway [12,27].…”

Section: Discussionsupporting

confidence: 92%

“…It is considered as effective monotherapy or adjunct therapy to levodopa [4][5][6][7]. Several in vitro and in vivo studies have reported that PPX may possess neuroprotective properties [8][9][10], and it has been suggested that the underlying neuroprotective mechanisms of PPX may be attributed by autoreceptor mediated DA turnover reduction, antioxidant action, anti-apoptosis, mitochondrial membrane potential stabilization, and up-regulation of brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) expression [8][9][10][11][12]. But even with all the reports from the above, it is still in debate whether the DA agonists are neuroprotective or not.…”

Section: Introductionmentioning

confidence: 99%

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Neuroprotection of Pramipexole in UPS Impairment Induced Animal Model of Parkinson’s Disease

Guo

Xie

et al. 2010

Neurochem Res

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Pramipexole (PPX), a dopamine (DA) receptor D3 preferring agonist, has been used as monotherapy or adjunct therapy to treat Parkinson's disease (PD) for many years. Several in vitro and in vivo studies in neurotoxin-induced DA neuron injury models have reported that PPX may possess neuroprotective properties. The present study is to evaluate the neuroprotection of PPX in a sustained DA neuron degeneration model of PD induced by ubiquitin-proteasome system (UPS) impairment. Adult C57BL/6 mice were treated with PPX (low dose 0.1 mg/kg or high dose 0.5 mg/kg, i.p, twice a day) started 7 days before, and continued after microinjection of proteasome inhibitor lactacystin in the medial forebrain bundle for a total 4 weeks. Animal behavior observation, and pathological and biochemical assays were conducted to determine the neuroprotective effects of PPX. We report here that PPX treatment significantly improves rotarod performance, attenuates DA neuron loss and striatal DA reduction, and alleviates proteasomal inhibition and microglial activation in the substantia nigra of lactacystin-lesioned mice. PPX can increase the levels of brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor and induce an activation of autophagy. Furthermore, pretreatment with D3 receptor antagonist U99194 can significantly block the PPX-mediated neuroprotection. These results suggest that multiple molecular pathways may be attributed to the neuroprotective effects of PPX in the UPS impairment model of PD.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Neuroprotection of Pramipexole in UPS Impairment Induced Animal Model of Parkinson’s Disease

Guo

Xie

et al. 2010

Neurochem Res

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“…Joyce and Millan (2007) proposed D3 receptor as key mediator for the protective and restorative effect of the DA agonists on dopaminergic neurons. This proposal was also based on the evidence that ropinirole and pramipexole slow the loss of dopaminergic cell terminals (and neurons) as measured using either F-DOPA PET or 123I-beta-CIT SPECT upon long-term administration to patients with PD when compared with l-DOPA treatment (Clarke and Guttman, 2002;Whone et al, 2003).…”

Section: Parkinson Disease: Possible Neurotrophic-like Effects Of D3 mentioning

confidence: 98%

Pharmacological targeting of dopamine D3 receptors: Possible clinical applications of selective drugs

Pich

Collo

2015

European Neuropsychopharmacology

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“…As recently summarized by Joyce and Millan [8], different D3 receptor-preferring agonists augment mitogenesis in the Sub Ventricular Zone and this effect may participate to the restoration of DAergic nigrostriatal pathway and locomotor activity in rat model of PD [9,10].…”

Section: Introductionmentioning

confidence: 97%

Dopaminergic Agonists: Possible Neurorescue Drugs Endowed with Independent and Synergistic Multisites of Action

et al. 2007

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Dopaminergic agonists have been usually used as adjunctive therapy for the cure of Parkinson's disease (PD). It is generally believed that treatment with these drugs is symptomatic rather then curative and does not stop or delay the progression of neuronal degeneration. However, several DA agonists of the DA D2-receptor family (including D2, D3 and D4-subtypes) have recently been shown to possess neuroprotective properties in different in vitro and in vivo experimental PD models. Here we summarize some recent data from our and other groups underlining the wide pharmacological spectrum of DA agonists currently used for treating PD patients. In particular, the mechanism of action of different DA agonists does not appear to be restricted to the stimulation of selective DA receptor subtypes being these drugs endowed with intrinsic, independent, and peculiar antioxidant effects. This activity may represent an additional pharmacological property contributing to their clinical efficacy in PD.

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Dopamine D3 receptor agonists for protection and repair in Parkinson's disease

Cited by 102 publications

References 46 publications

Neuroprotection of Pramipexole in UPS Impairment Induced Animal Model of Parkinson’s Disease

Neuroprotection of Pramipexole in UPS Impairment Induced Animal Model of Parkinson’s Disease

Pharmacological targeting of dopamine D3 receptors: Possible clinical applications of selective drugs

Dopaminergic Agonists: Possible Neurorescue Drugs Endowed with Independent and Synergistic Multisites of Action

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