New Insights on the Role of Bioactive Food Derivatives in Neurodegeneration and Neuroprotection.

Over the last three decades, neurodegenerative diseases have received increasing attention due to their frequency in the aging population and the social and economic burdens they are posing. In parallel, an era's worth of research in neuroscience has shaped our current appreciation of the complex relationship between nutrition and the central nervous system. Particular branches of nutrition continue to galvanize neuroscientists, in particular the diverse roles that bioactive food derivatives play on health and disease.

Activation of Antioxidant and Proteolytic Pathways in the Nigrostriatal Dopaminergic System After 3,4-Methylenedioxymethamphetamine Administration: Sex-Related Differences.

3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") is an amphetamine-related drug that may damage the dopaminergic nigrostriatal system. To investigate the mechanisms that sustain this toxic effect and ascertain their sex-dependence, we evaluated in the nigrostriatal system of MDMA-treated (4 × 20 mg/kg, 2 h apart) male and female mice the activity of superoxide dismutase (SOD), the gene expression of SOD type 1 and 2, together with SOD1/2 co-localization with tyrosine hydroxylase (TH)-positive neurons. In the same mice and brain areas, activity of glutathione peroxidase (GPx) and of β2/β5 subunits of the ubiquitin-proteasome system (UPS) were also evaluated.

Anti-Apoptotic and Anti-Inflammatory Role of Trans ε-Viniferin in a Neuron-Glia Co-Culture Cellular Model of Parkinson's Disease.

The polyphenol trans-ε-viniferin (viniferin) is a dimer of resveratrol, reported to hold antioxidant and anti-inflammatory properties. The aims of our study were to evaluate the neuroprotective potential of viniferin in the nerve growth factor (NGF)-differentiated PC12 cells, a dopaminergic cellular model of Parkinson's disease (PD) and assess its anti-inflammatory properties in a N9 microglia-neuronal PC12 cell co-culture system. The neuronal cells were pre-treated with viniferin, resveratrol or their mixture before the administration of 6-hydroxydopamine (6-OHDA), recognized to induce parkinsonism in rats.

The Neuroinflammatory and Neurotoxic Potential of Palmitic Acid Is Mitigated by Oleic Acid in Microglial Cells and Microglial-Neuronal Co-cultures.

Neuroinflammation has been implicated in the pathogenesis of neurodegeneration and is now accepted as a common molecular feature underpinning neuronal damage and death. Palmitic acid (PA) may represent one of the links between diet and neuroinflammation. The aims of this study were to assess whether PA induced toxicity in neuronal cells by modulating microglial inflammatory responses and/or by directly targeting neurons.

Diabetes, a Contemporary Risk for Parkinson's Disease: Epidemiological and Cellular Evidences.

Diabetes mellitus (DM), a group of diseases characterized by defective glucose metabolism, is the most widespread metabolic disorder affecting over 400 million adults worldwide. This pathological condition has been implicated in the pathogenesis of a number of central encephalopathies and peripheral neuropathies. In further support of this notion, recent epidemiological evidence suggests a link between DM and Parkinson's disease (PD), with hyperglycemia emerging as one of the culprits in neurodegeneration involving the nigrostriatal pathway, the neuroanatomical substrate of the motor symptoms affecting parkinsonian patients.

Considerations for the Use of Polyphenols as Therapies in Neurodegenerative Diseases.

Over the last two decades, the increase in the incidence of neurodegenerative diseases due to the increasingly ageing population has resulted in a major social and economic burden. At present, a large body of literature supports the potential use of functional nutrients, which exhibit potential neuroprotective properties to mitigate these diseases. Among the most studied dietary molecules, polyphenols stand out because of their multiple and often overlapping reported modes of action.

Dopaminergic neurodegeneration in a rat model of long-term hyperglycemia: preferential degeneration of the nigrostriatal motor pathway.

Epidemiological evidence suggests a correlation between diabetes and age-related neurodegenerative disorders, including Alzheimer's and Parkinson's diseases. Hyperglycemia causes oxidative stress in vulnerable tissues such as the brain. We recently demonstrated that elevated levels of glucose lead to the death of dopaminergic neurons in culture through oxidative mechanisms.

Sympathetic regulation and anterior cingulate cortex volume are altered in a rat model of chronic back pain.

Chronic pain is associated with autonomic disturbance. However, specific effects of chronic back pain on sympathetic regulation remain unknown. Chronic pain is also associated with structural changes in the anterior cingulate cortex (ACC), which may be linked to sympathetic dysregulation.

Oleuropein Prevents Neuronal Death, Mitigates Mitochondrial Superoxide Production and Modulates Autophagy in a Dopaminergic Cellular Model.

Parkinson's disease (PD) is a progressive neurodegenerative disorder, primarily affecting dopaminergic neurons in the substantia nigra. There is currently no cure for PD and present medications aim to alleviate clinical symptoms, thus prevention remains the ideal strategy to reduce the prevalence of this disease. The goal of this study was to investigate whether oleuropein (OLE), the major phenolic compound in olive derivatives, may prevent neuronal degeneration in a cellular dopaminergic model of PD, differentiated PC12 cells exposed to the potent parkinsonian toxin 6-hydroxydopamine (6-OHDA).

Development of an Insert Co-culture System of Two Cellular Types in the Absence of Cell-Cell Contact.

The role of secreted soluble factors in the modification of cellular responses is a recurrent theme in the study of all tissues and systems. In an attempt to make straightforward the very complex relationships between the several cellular subtypes that compose multicellular organisms, in vitro techniques have been developed to help researchers acquire a detailed understanding of single cell populations. One of these techniques uses inserts with a permeable membrane allowing secreted soluble factors to diffuse.

[Neuroinflammation: Dr Jekyll or Mr Hyde?].

Sheltered in a bony cage, populated by cells with little regenerative potential, the central nervous system (CNS) could likely not withstand classic inflammation without risking major sequelae. As a consequence, it had to develop an original way to provide surveillance, defence and reparation, which relies on both the complex architecture of the periphery-nervous parenchyma exchange zones, and the tightly regulated collaboration between all the cell populations that reside in or pass through the CNS. Despite its tight regulation, neuroinflammation is sometimes the cause of irreversible loss but it is also where the solution stands.

Cucurbitacin E, An Experimental Lead Triterpenoid with Anticancer, Immunomodulatory and Novel Effects Against Degenerative Diseases. A Mini-Review.

A growing number of studies have revealed that natural molecules own interesting antioxidant and anti-apoptotic properties in cell culture as well as in animal models of human diseases such as cancer, inflammatory and neurodegenerative diseases. During the past sixty years, several cucurbitacins have been isolated from a number of cucurbitaceous species, amongst others. Cucurbitacins are triterpenoid compounds originally identify as the bitter components of the Cucurbit family that demonstrated several pro-survival activities in various model of cellular decay.

Epigallocatechin-3-Gallate, a Promising Molecule for Parkinson's Disease?

Parkinson's disease (PD) is the second most common neurodegenerative disease, and it is characterized by the loss of the neurotransmitter dopamine and neuronal degeneration in the substantia nigra pars compacta. Thus far, current therapeutic strategies have failed to address neuronal degeneration. It has been reported that overproduction of reactive oxygen species, resulting in oxidative stress, and neuroinflammation play an important role in neurodegenerative diseases through the induction of macromolecular oxidative damage and modulation of intracellular signaling pathways concurring to neuronal cell death.

Cucurbitacin E has neuroprotective properties and autophagic modulating activities on dopaminergic neurons.

Natural molecules are under intensive study for their potential as preventive and/or adjuvant therapies for neurodegenerative disorders such as Parkinson's disease (PD). We evaluated the neuroprotective potential of cucurbitacin E (CuE), a tetracyclic triterpenoid phytosterol extracted from the Ecballium elaterium (Cucurbitaceae), using a known cellular model of PD, NGF-differentiated PC12. In our postmitotic experimental paradigm, neuronal cells were treated with the parkinsonian toxin 1-methyl-4-phenylpyridinium (MPP(+)) to provoke significant cellular damage and apoptosis or with the potent N,N-diethyldithiocarbamate (DDC) to induce superoxide (O2(•-)) production, and CuE was administered prior to and during the neurotoxic treatment.

Resveratrol as a protective molecule for neuroinflammation: a review of mechanisms.

Under normal conditions, most of the central nervous system (CNS) is protected by the blood brain barrier (BBB) from systemic inflammation progression and from the infiltration of immune cells. As a consequence, the CNS developed an original way to provide surveillance, defense and repair, which relies on the complex process of neuroinflammation. Despite tight regulation, neuroinflammation is frequently the cause of irreversible nerve cell loss but it is also where the solution lies.

17β-estradiol delays 6-OHDA-induced apoptosis by acting on Nur77 translocation from the nucleus to the cytoplasm.

Nuclear receptors (Nurs) represent a large family of gene expression regulating proteins. Gathering evidence indicates an important role for Nurs as transcription factors in dopamine neurotransmission. Nur77, a member of the Nur superfamily, plays a role in mediating the effects of antiparkinsonian and neuroleptic drugs.

Resveratrol protects DAergic PC12 cells from high glucose-induced oxidative stress and apoptosis: effect on p53 and GRP75 localization.

Resveratrol (RESV), a polyphenolic natural compound, has long been acknowledged to have cardioprotective and antiinflammatory actions. Evidence suggests that RESV has antioxidant properties that reduce the formation of reactive oxygen species leading to oxidative stress and apoptotic death of dopaminergic (DAergic) neurons in Parkinson's disease (PD). Recent literature has recognized hyperglycemia as a cause of oxidative stress reported to be harmful for the nervous system.

Quercetin and sesamin protect dopaminergic cells from MPP+-induced neuroinflammation in a microglial (N9)-neuronal (PC12) coculture system.

A growing body of evidence indicates that the majority of Parkinson's disease (PD) cases are associated with microglia activation with resultant elevation of various inflammatory mediators and neuroinflammation. In this study, we investigated the effects of 2 natural molecules, quercetin and sesamin, on neuroinflammation induced by the Parkinsonian toxin 1-methyl-4-phenylpyridinium (MPP(+)) in a glial-neuronal system. We first established that quercetin and sesamin defend microglial cells against MPP(+)-induced increases in the mRNA or protein levels of 3 pro-inflammatory cytokines (interleukin-6, IL-1β and tumor necrosis factor-alpha), as revealed by real time-quantitative polymerase chain reaction and enzyme-linked immunoabsorbent assay, respectively.

Quercetin and sesamin protect neuronal PC12 cells from high-glucose-induced oxidation, nitrosative stress, and apoptosis.

Complications of diabetes are now well-known to affect sensory, motor, and autonomic nerves. Diabetes is also thought to be involved in neurodegenerative processes characteristic of several neurodegenerative diseases. Indeed, it has been acknowledged recently that hyperglycemia-induced oxidative stress contributes to numerous cellular reactions typical of central nervous system deterioration.

Brassinosteroids and analogs as neuroprotectors: synthesis and structure-activity relationships.

We have demonstrated previously that the brassinosteroid (BR) 24-epibrassinolide exerts neuroprotective effects deriving from its antioxidative properties. In this study, we synthesized 2 natural BRs and 5 synthetic analogs and analyzed their neuroprotective actions in neuronal PC12 cells, against 1-methyl-4-phenylpyridinium (MPP(+)), a neurotoxin known to induce oxidative stress and degenerescence of dopaminergic neurons characteristic of Parkinsonian brains. We also tested the neuroprotective potential of 2 commercially available BRs.

24-Epibrassinolide, a Phytosterol from the Brassinosteroid Family, Protects Dopaminergic Cells against MPP-Induced Oxidative Stress and Apoptosis.

Oxidative stress and apoptosis are frequently cited to explain neuronal cell damage in various neurodegenerative disorders, such as Parkinson' s disease. Brassinosteroids (BRs) are phytosterols recognized to promote stress tolerance of vegetables via modulation of the antioxidative enzyme cascade. However, their antioxidative effects on mammalian neuronal cells have never been examined so far.

Sesamin modulates tyrosine hydroxylase, superoxide dismutase, catalase, inducible NO synthase and interleukin-6 expression in dopaminergic cells under MPP+-induced oxidative stress.

Oxidative stress is regarded as a mediator of nerve cell death in several neurodegenerative disorders, such as Parkinson's disease. Sesamin, a lignan mainly found in sesame oil, is currently under study for its anti-oxidative and possible neuroprotective properties. We used 1-methyl-4-phenyl-pyridine (MPP(+)) ion, the active metabolite of the potent parkinsonism-causing toxin 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine, to produce oxidative stress and neurodegeneration in neuronal PC12 cells, which express dopamine, as well as neurofilaments.

Protective effects of resveratrol and quercetin against MPP+ -induced oxidative stress act by modulating markers of apoptotic death in dopaminergic neurons.

Reactive oxygen species produced by oxidative stress may participate in the apoptotic death of dopamine neurons distinctive of Parkinson's disease. Resveratrol, a red wine extract, and quercetin, found mainly in green tea, are two natural polyphenols, presenting antioxidant properties in a variety of cellular paradigms. The aim of this study was to evaluate the effect of resveratrol and quercetin on the apoptotic cascade induced by the administration of 1-methyl-4-phenylpyridinium ion (MPP(+)), a Parkinsonian toxin, provoking the selective degeneration of dopaminergic neurons.