PPAR-α agonist fenofibrate protects against the damaging effects of MPTP in a rat model of Parkinson's disease

Barbiero, Janaína K.; Santiago, Ronise Martins; Tonin, Fernanda S.; Boschen, Suelen Lúcio; Silva, Luísa Mota da; Werner, Maria Fernanda de Paula; Cunha, Cláudio Da; Lima, Marcelo M.S.; Vital, Maria A.B.F.

doi:10.1016/j.pnpbp.2014.02.009

Cited by 80 publications

(47 citation statements)

References 84 publications

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“…NEAT1 showed highly variable expression levels in the SN, which may reflect its reaction to a wide variety of stimuli, including estrogen (25), hepatic fibrosis (59), oxidative stress, and treatment with various therapeutics including simvastatin and fenofibrate (this study)—possibly through the effects of these drugs on the activity of transcription factors of the PPAR family (60, 61), binding sites for which and for their interactor retinoid X receptor-α lie upstream to the NEAT1 transcription start site (47, 62). This offers another mechanism to explain the neuroprotective traits of these drugs (16, 60, 63, 64) and calls for investigating the effects of additional blood-brain barrier–penetrable agents on NEAT1 levels.…”

Section: Discussionmentioning

confidence: 90%

“…This offers another mechanism to explain the neuroprotective traits of these drugs (16, 60, 63, 64) and calls for investigating the effects of additional blood-brain barrier–penetrable agents on NEAT1 levels. However, although simvastatin and fenofibrate elevate NEAT1 expression, other widely used drugs may suppress its expression, which could be harmful in particular patients with PD, such as carriers of the LRRK2 mutation.…”

Section: Discussionmentioning

confidence: 99%

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NEAT1 is overexpressed in Parkinson's disease substantia nigra and confers drug‐inducible neuroprotection from oxidative stress

et al. 2019

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Recent reports attribute numerous regulatory functions to the nuclear paraspeckle‐forming long non‐coding RNA, nuclear enriched assembly transcript 1 (NEAT1), but the implications of its involvement in Parkinson's disease (PD) remain controversial. To address this issue, we assessed NEAT1 expression levels and cell type patterns in the substantia nigra (SN) from 53 donors with and without PD, as well as in interference tissue culture tests followed by multiple in‐house and web‐available models of PD. PCR quantification identified elevated levels of NEAT1 expression in the PD SN compared with control brains, an elevation that was reproducible across a multitude of disease models. In situ RNA hybridization supported neuron‐specific formation of NEATl‐based para‐speckles at the SN and demonstrated coincreases of NEAT1 and paraspeckles in cultured cells under paraquat (PQ)‐induced oxidative stress. Furthermore, neuroprotective agents, including fenofibrate and simvastatin, induced NEAT1 up‐regulation, whereas RNA interference—mediated depletion of NEAT1 exacerbated death of PQ‐exposed cells in a leucine‐rich repeat kinase 2‐mediated manner. Our findings highlight a novel protective role for NEAT1 in PD and suggest a previously unknown mechanism for the neuroprotective traits of widely used preventive therapeutics.—Simchovitz, A., Hanan, M., Niederhoffer, N., Madrer, N., Yayon, N., Bennett, E. R., Greenberg, D. S., Kadener, S., Soreq, H. NEAT1 is overexpressed in Parkinson's disease substantia nigra and confers drug‐inducible neuroprotection from oxidative stress. FASEB J. 33, 11223–11234 (2019). http://www.fasebj.org

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

NEAT1 is overexpressed in Parkinson's disease substantia nigra and confers drug‐inducible neuroprotection from oxidative stress

et al. 2019

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“…In addition, the issue of DA depletion resulting in depressive behavior must also be taken into consideration in the current study, as reported by others using a more acute MPTP model of PD (Barbeiro et al, 2014; Castro et al, 2013). Although this behavior was not measured, there was no overall change in locomotor behavior, only changes in several measures of gait, following chronic/progressive treatment with MPTP compared to a significant decrease in motor behavior following acute MPTP administration (Fisher et al, 2004).…”

Section: Discussionmentioning

confidence: 94%

Executive function deficits and glutamatergic protein alterations in a progressive 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine mouse model of Parkinson's disease

Pflibsen

Stang

Sconce

et al. 2015

J of Neuroscience Research

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Changes within executive function are at the root of most cognitive problems associated with Parkinson’s disease (PD). Because dopaminergic treatment does not necessarily alleviate deficits in executive function, it has been hypothesized that dysfunction of other neurotransmitters/systems besides dopamine (DA), maybe associated with this decrease in cognitive function. We have reported decreases in motor-function and dopaminergic/glutamatergic biomarkers using a progressive 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) Parkinson’s mouse model. Assessment of executive function and dopaminergic/glutamatergic biomarkers within the limbic circuit has previously not been explored in our model. Our results show progressive behavioral decline in cued response task (a rodent model for frontal cortex cognitive function) with increasing weekly doses of MPTP. Although within the dorsolateral (DL) striatum mice administered MPTP showed a 63% and 83% loss of tyrosine hydroxylase (TH) and dopamine transporter (DAT) expression, respectively, there were no changes in the nucleus accumbens (NAc) or medial prefrontal cortex (mPFC). Furthermore, dopamine-1 receptor (DA-D1) and vesicular glutamate transporter-1 (VGLUT-1) expression increased in the mPFC following DA loss. There was a significant MPTP-induced decrease/increase in VGLUT-1 and vesicular glutamate transporter-2 (VGLUT-2) expression, respectively, within the DL striatum. We propose that the behavioral decline following MPTP treatment may be associated with a change in not only cortical-cortical (VGLUT-1) glutamate function, but also in striatal DA and glutamate (VGLUT-1/VGLUT-2) input.

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“…Interestingly, a PPAR-α receptor agonist was able to confer neuroprotection in an experimental model of PD [34].…”

Section: Discussionmentioning

confidence: 99%

Inverse association between yerba mate consumption and idiopathic Parkinson's disease. A case–control study

Gatto

Melcon²,

Parisi

et al. 2015

Journal of the Neurological Sciences

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PPAR-α agonist fenofibrate protects against the damaging effects of MPTP in a rat model of Parkinson's disease

Cited by 80 publications

References 84 publications

NEAT1 is overexpressed in Parkinson's disease substantia nigra and confers drug‐inducible neuroprotection from oxidative stress

NEAT1 is overexpressed in Parkinson's disease substantia nigra and confers drug‐inducible neuroprotection from oxidative stress

Executive function deficits and glutamatergic protein alterations in a progressive 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine mouse model of Parkinson's disease

Inverse association between yerba mate consumption and idiopathic Parkinson's disease. A case–control study

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