Novel pharmacological targets for the treatment of Parkinson's disease

Schapira, Anthony H.V.; Bézard, Erwan; Brotchie, Jonathan M.; Calon, Frédéric; Collingridge, Graham L.; Ferger, B.; Hengerer, Bastian; Hirsch, Étienne C.; Jenner, Peter; Novère, Nicolas Le; Obeso, José A.; Schwarzschild, Michael A.; Spampinato, Umberto; Davidai, Giora

doi:10.1038/nrd2087

Cited by 269 publications

(151 citation statements)

References 114 publications

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“…In the next few years, we believe that novel approaches (Di Giovanni et al, 2006;Schapira et al, 2006) will support the current dopamine-replacement therapy for PD. Furthermore, early diagnosis, early symptomatic treatment and particularly the introduction of neuroprotective therapies will improve PD pharmacological management, as disease modification remains the most important goal in PD.…”

Section: Discussionmentioning

confidence: 99%

Non-steroidal anti-inflammatory drugs in Parkinson's disease

Esposito

Matteo

Benigno

et al. 2007

Experimental Neurology

218

176

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Parkinson's disease (PD) is known to be a chronic and progressive neurodegenerative disease caused by a selective degeneration of dopaminergic (DAergic) neurons in the substantia nigra pars compacta (SNc). A large body of experimental evidence indicates that the factors involved in the pathogenesis of this disease are several, occurring inside and outside the DAergic neuron. Recently, the role of the neuron-glia interaction and the inflammatory process, in particular, has been the object of intense study by the research community. It seems to represent a new therapeutic approach opportunity for this neurological disorder. Indeed, it has been demonstrated that the cyclooxygenase type 2 (COX-2) is upregulated in SNc DAergic neurons in both PD patients and animal models of PD and, furthermore, non-steroidal anti-inflammatory drugs (NSAIDs) pre-treatment protects against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or 6 hydroxydopamine (6-OHDA)-induced nigrostriatal dopamine degeneration. Moreover, recent epidemiological studies have revealed that the risk of developing PD is reduced in humans who make therapeutical use of NSAIDs. Consequently, it is hypothesized that they might delay or prevent the onset of PD. However, whether or not these common drugs may also be of benefit to those individuals who already have Parkinson's disease has not as yet been shown.In this paper, evidence relating to the protective effects of aspirin or other NSAIDs on DAergic neurons in animal models of Parkinson's disease will be discussed. In addition, the pharmacological mechanisms by which these molecules can exert their neuroprotective effects will be reviewed. Finally, epidemiological data exploring the effectiveness of NSAIDs in the prevention of PD and their possible use as adjuvants in the therapy of this neurodegenerative disease will also be examined.

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Section: Discussionmentioning

confidence: 99%

Non-steroidal anti-inflammatory drugs in Parkinson's disease

Esposito

Matteo

Benigno

et al. 2007

Experimental Neurology

218

176

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“…Most of the already reported allelochemicals from medicinal plants also have reported therapeutics properties. For example, the allelochemical artemisinin is used in an anti-malarial drug [17], safranal; anticonvulsant [18], L-3,4-dihydroxyphenylalanine (L-DOPA); anti-Parkinson's disease [145], kaempferol; and anti-cancer [19], among a tall list of others. Although some of the species showed significant inhibition by both leachates and volatile constituents, there was no significant correlation between them.…”

Section: Correlation Between Ethnobotanical Indices and Allelopathic mentioning

confidence: 99%

Exploring Alternative Use of Medicinal Plants for Sustainable Weed Management

et al. 2017

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This paper presents the first application of ethnobotanical studies to screen for allelopathic species among medicinal plants for sustainable weed management. This study assesses the possible relationship between ethnobotanical indices and allelopathy of medicinal plants. Ethnobotanical data were collected in 2016 by using semi-structured interviews with 140 informants in the Ejisu-Juaben Municipality, Ghana. Data were analysed using statistical tool and ethnobotanical indices including use value (UV), Fidelity Level (FL), Relative Frequency of Citation (RFC). The Sandwich and Dish pack methods were respectively used to evaluate allelopathy through leachates and volatiles of collected samples. Ninety-five species belonging to 43 families are reported in this study, with leaves (52%) cited the most utilised plant part. Cleistopholis patens (UV = 0.54; FL = 90.7%; RFC = 0.37) and Ocimum gratissimum (UV = 0.37; FL = 38.4%; RFC = 0.35) were among the most cited species. Thirty-two species showed inhibition (≥49.3%) by leachates, while twenty-four species were found with potential volatile inhibitory compounds against lettuce radicle growth. There was a significant positive correlation (Pearson) between the UV and RFC of medicinal plants and allelopathy by leaf leachates (r = 0.639 **; p = 0.01 and r = 0.653 **; p = 0.01 respectively). This systematic documentation of medicinal plants in Ejisu-Juaben Municipality shows medicinal plants with ethnomedicinal values and potential allelopathy that can be utilised in sustainable weed control.

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“…Besides roles in other cellular pathways, Parkin has an essential function in mitochondrial homeostasis and quality control. Mitochondria as the energy producing organelle can be damaged either by the production of reactive oxygen species by faulty oxidative phosphorylation (Han et al, 2001) or by several environmental toxins (Schapira et al, 2006). The accumulation of oxidative damage can be prevented by the selection and degradation of fissioned non-functional mitochondria by an autophagic mechanism termed mitophagy (Narendra et al, 2008;Twig et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

UBE2N, UBE2L3 and UBE2D2/3 ubiquitin-conjugating enzymes are essential for parkin-dependent mitophagy

Geisler

Vollmer

Golombek

et al. 2014

Journal of Cell Science

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Depolarized mitochondria are degraded by mitophagy in a process that depends on the Parkinson's disease gene products PINK1 and Parkin. This is accompanied by ubiquitylation of several mitochondrial substrates. The roles of E2 ubiquitin-conjugating enzymes (UBE2) in mitophagy are poorly understood. Here, we investigate a set of UBE2 enzymes that might regulate Parkinmediated mitophagy. Knockdown of the E2 enzymes UBE2N, UBE2L3 or UBE2D2 and UBE2D3 (UBE2D2/3) significantly reduced autophagic clearance of depolarized mitochondria. However, this did not interfere with mitochondrial PINK1 stabilization and Parkin translocation. UBE2N knockdown prevented specifically K63-linked ubiquitylation at mitochondrial sites. Nevertheless, polyubiquitin and p62 (officially known as SQSTM1) were still found on mitochondria after individual UBE2 knockdown. Knockdown of all of these UBE2s together significantly reduced mitochondrial polyubiquitylation and p62 recruitment. Moreover, reduced ubiquitylation of mitofusins, the mitochondrial import receptor subunits TOM20 and TOM70, the voltagedependent anion channel protein 1 and Parkin was observed in cells silenced for all of these UBE2s. A version of Parkin with a mutation in the active site (C431S) failed to ubiquitylate these mitochondrial substrates even in the presence of UBE2s. We conclude that UBE2N, UBE2L3 and UBE2D2/3 synergistically contribute to Parkin-mediated mitophagy.

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Novel pharmacological targets for the treatment of Parkinson's disease

Cited by 269 publications

References 114 publications

Non-steroidal anti-inflammatory drugs in Parkinson's disease

Non-steroidal anti-inflammatory drugs in Parkinson's disease

Exploring Alternative Use of Medicinal Plants for Sustainable Weed Management

UBE2N, UBE2L3 and UBE2D2/3 ubiquitin-conjugating enzymes are essential for parkin-dependent mitophagy

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