Progress in Parkinson's disease—Where do we stand?

Toulouse, André; Sullivan, Aideen M.

doi:10.1016/j.pneurobio.2008.05.003

Cited by 170 publications

(115 citation statements)

References 296 publications

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“…Patients with PD lack effective therapies that halt neurodegenerative processes and can only be treated for clinical symptoms [23], reinforcing the need to better understand the biological processes that underlie the neurodegeneration [24]. Increasing evidence suggests that salidroside reduces the levels of ROS, which have been linked to the pathogenesis of many diseases [25] including diabetes, cardiovascular disease, and degenerative disease.…”

Section: Discussionmentioning

confidence: 99%

Salidroside Protects Against 6-Hydroxydopamine-Induced Cytotoxicity by Attenuating ER Stress

et al. 2016

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Parkinson's disease (PD) is a neurodegenerative disease characterized by a persistent decline of dopaminergic (DA) neurons in the substantia nigra pars compacta. Despite its frequency, effective therapeutic strategies that halt the neurodegenerative processes are lacking, reinforcing the need to better understand the molecular drivers of this disease. Importantly, increasing evidence suggests that the endoplasmic reticulum (ER) stress-induced unfolded protein response is likely involved in DA neuronal death. Salidroside, a major compound isolated from Rhodiola rosea L., possesses potent antioxidative stress properties and protects against DA neuronal death. However, the underlying mechanisms are not well understood. In the present study, we demonstrate that salidroside prevents 6-hydroxydopamine (6-OHDA)-induced cytotoxicity by attenuating ER stress. Furthermore, treatment of a DA neuronal cell line (SN4741) and primary cortical neurons with salidroside significantly reduced neurotoxin-induced increases in cytoplasmic reactive oxygen species and calcium, both of which cause ER stress, and cleaved caspase-12, which is responsible for ER stress-induced cell death. Together, these results suggest that salidroside protects SN4741 cells and primary cortical neurons from 6-OHDA-induced neurotoxicity by attenuating ER stress. This provides a rationale for the investigation of salidroside as a potential therapeutic agent in animal models of PD.

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Section: Discussionmentioning

confidence: 99%

Salidroside Protects Against 6-Hydroxydopamine-Induced Cytotoxicity by Attenuating ER Stress

et al. 2016

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“…As life expectancy is significantly increasing in the Western world, the incidence of PD is steadily escalating. Consequently, the financial and economical burden of the treatment and care of PD patients is substantial and increasing [1]. Thus, research on the causes of this debilitating disease is critical, as is the development of new treatments.…”

Section: Parkinson's Diseasementioning

confidence: 99%

“…Surgical methods involving ablation of deep brain structures or deep brain stimulation have also been used with good success, but these procedures are not widelyavailable or applicable for all patients. In summary, none of the current treatments provide safe and long-lasting relief from the symptoms and have little or no effect on the progression of the disease [1]. Current research is aimed at developing therapies that will halt the neurodegenerative process, rather than simply treat the symptoms.…”

Section: Parkinson's Diseasementioning

confidence: 99%

Neurotrophic factors for the treatment of Parkinson's disease

Sullivan

Toulouse

2011

Cytokine & Growth Factor Reviews

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“…The overabundance of free radicals may damage cell lipids, proteins and DNA (Shimizu et al, 2002). Several of the genes linked to familial forms of Parkinson's disease appear to be involved in the protection against or the propagation of oxidative stress (Toulouse and Sullivan, 2008;Yacoubian and Standaert, 2009). Among the ROS, the hydroxyl radical is the most reactive and destructive free radical.…”

Section: Abbreviationsmentioning

confidence: 99%

Acute versus long-term effects of 6-hydroxydopamine on oxidative stress and dopamine depletion in the striatum of mice

Varcin

Bentea

Mertens

et al. 2011

Journal of Neuroscience Methods

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Oxidative stress is one of the mechanisms which may be important in the pathogenesis of Parkinson's disease. In the current study, the effects of 6-hydroxydopamine (6-OHDA) perfusion on hydroxyl radical formation in the mouse striatum were investigated using the in vivo salicylate trapping microdialysis technique. The latter uses salicylate as a trapping agent for hydroxyl radicals with formation of 2,3-dihydroxybenzoic acid (2,3-DHBA), which is measured by HPLC. Two different approaches of the technique were validated in mice. First, perfusion of the trapping agent salicylate (1 mM) via the probe in combination with 6-OHDA (5 M) was used to screen for radical scavenging properties of compounds in mice. Alternatively, striatal administration of 6-OHDA in a concentration known to induce nigrostriatal denervation (1 mM), without the trapping agent, allowed to maximally challenge the neuronal microenvironment and as such to investigate both its acute and long-term effects. In the first method, as expected, glutathione (GSH) (1.5 mM) prevented the 6-OHDA-induced increase in 2,3-DHBA levels. In the second method, GSH prevented the hydroxyl radical formation, while depletion of GSH with 2-cyclohexen-1-one (CHO) resulted in significantly higher 2,3-DHBA levels than when 6-OHDA was perfused alone. Three weeks after the local 6-OHDA perfusion, the total striatal dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) content were reduced by 30%, compared to the intact striatum, accompanied by a reduction in striatal tyrosine hydroxylase (TH) immunoreactive (ir) nerve terminals. This suggests that the second method can be used to determine the acute as well as the long-term effects of 6-OHDA in the mouse striatum.

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Progress in Parkinson's disease—Where do we stand?

Cited by 170 publications

References 296 publications

Salidroside Protects Against 6-Hydroxydopamine-Induced Cytotoxicity by Attenuating ER Stress

Salidroside Protects Against 6-Hydroxydopamine-Induced Cytotoxicity by Attenuating ER Stress

Neurotrophic factors for the treatment of Parkinson's disease

Acute versus long-term effects of 6-hydroxydopamine on oxidative stress and dopamine depletion in the striatum of mice

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