Glucocorticoid receptor–nitric oxide crosstalk and vulnerability to experimental parkinsonism: pivotal role for glia–neuron interactions

Marchetti, Bianca; Serra, Pier Andrea; Tirolo, Cataldo; L’Episcopo, Francesca; Caniglia, Salvatore; Gennuso, Florinda; Testa, Nuccio; Miele, E; Desole, Speranza; Barden, Nicholas; Morale, Maria Concetta

doi:10.1016/j.brainresrev.2004.12.030

Cited by 55 publications

(78 citation statements)

References 132 publications

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“…In addition to oxidative stress also other mechanisms have been proposed to be involved in selective DA neuron degeneration in PD, including excitotoxicity, intracellular calcium and metal ion rise, neurofibrillary tangle formation and disruption of the cytoskeletal transport [112]. More recently, neuroinflammation and microglial activation have been implicated in the neurodegenerative process in PD, as initially suggested by McGeer et al [155] and then by several authors ( [77,89,95,97,104,102,107,148,168]). In fact, studies accumulated over the last two decades have clearly indicated the presence of an abnormal glial response in postmortem nervous system of PD patients.…”

Section: Parkinson's Disease and Neuroinflammationmentioning

confidence: 95%

Estrogen anti-inflammatory activity in brain: A therapeutic opportunity for menopause and neurodegenerative diseases

Vegeto

Benedusi

Maggi

2008

Frontiers in Neuroendocrinology

273

206

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a b s t r a c tRecent studies highlight the prominent role played by estrogens in protecting the central nervous system (CNS) against the noxious consequences of a chronic inflammatory reaction. The neurodegenerative process of several CNS diseases, including Multiple Sclerosis, Alzheimer's and Parkinson's Diseases, is associated with the activation of microglia cells, which drive the resident inflammatory response. Chronically stimulated during neurodegeneration, microglia cells are thought to provide detrimental effects on surrounding neurons. The inhibitory activity of estrogens on neuroinflammation and specifically on microglia might thus be considered as a beneficial therapeutic opportunity for delaying the onset or progression of neurodegenerative diseases; in addition, understanding the peculiar activity of this female hormone on inflammatory signalling pathways will possibly lead to the development of selected anti-inflammatory molecules. This review summarises the evidence for the involvement of microglia in neuroinflammation and the anti-inflammatory activity played by estrogens specifically in microglia.

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Section: Parkinson's Disease and Neuroinflammationmentioning

confidence: 95%

Estrogen anti-inflammatory activity in brain: A therapeutic opportunity for menopause and neurodegenerative diseases

Vegeto

Benedusi

Maggi

2008

Frontiers in Neuroendocrinology

273

206

View full text Add to dashboard Cite

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“…Increasing evidence suggests that the inducible isoform of nitric-oxide synthase (iNOS) is instrumental in the neuropathogenesis associated with infection (Poluektova et al 2005) trauma (Louin et al 2006) and neurodegenerative diseases (Marchetti et al 2005). While not typically expressed in the central nervous system (CNS) under physiological conditions, iNOS is transcriptionally induced by various stimuli associated with pathologic insults including, hypoxia, bacterial components, viral proteins, and cytokines.…”

Section: Introductionmentioning

confidence: 99%

β-Funaltrexamine Inhibits Inducible Nitric-oxide Synthase Expression in Human Astroglial Cells

Davis

Buck

Saffarian

et al. 2008

J Neuroimmune Pharmacol

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The inducible isoform of nitric-oxide synthase (iNOS) is involved in neuropathogenesis associated with infection and disease in the brain. Hence, there is considerable interest in the identification of therapeutic interventions to prevent iNOS-mediated pathology. Astroglia are a major site of iNOS expression during neuropathogenesis. To mimic a key component of neuroinflammation, human A172 astroglial cells were exposed in vitro to a cytokine mixture containing interferon γ, tumor necrosis factor α, and interleukin-1β, resulting in significant iNOS expression. Next, we assessed the effects of the mu opioid receptor antagonist, β-funaltrexamine (β-FNA), on cytokine induced iNOS expression in human astroglia. β-FNA dose-dependently inhibited iNOS expression. β-FNA transcriptionally (or pre-transcriptionally) inhibited cytokine-induced iNOS activation as indicated by a significant decrease in NOS2 messenger RNA expression. Further characterization of the novel, anti-inflammatory actions of β-FNA may provide insights for pharmacologic strategies to treat or prevent brain pathologies associated with neuroinflammation.

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“…Under normal conditions, astrocytes exert a fundamental protective function against oxidative stress, and the interaction between astrocytes and neurons has been variously demonstrated to exert striking neurotrophic, differentiation, and neuroprotective effects (Takeshima et al 1994;McNaught and Jenner 1999;Marchetti et al 2005). However, under conditions of chronic inflammatory stress, activated astrocytes and microglia may become dysfunctional and overexpress a variety of cytotoxic mediators eventually resulting in dopaminergic neuron death (Morale et al 2006).…”

Section: The Concept Of Immunomodulationmentioning

confidence: 98%

“…Recent evidence clearly indicates that neuroinflammatory mechanisms may play an important role in the pathogenesis of PD (Hunot and Hirsch 2003;McGeer and McGeer 2004;Marchetti et al 2005). Under normal conditions, astrocytes exert a fundamental protective function against oxidative stress, and the interaction between astrocytes and neurons has been variously demonstrated to exert striking neurotrophic, differentiation, and neuroprotective effects (Takeshima et al 1994;McNaught and Jenner 1999;Marchetti et al 2005).…”

Section: The Concept Of Immunomodulationmentioning

confidence: 99%

Autotransplantation of Bone Marrow-Derived Stem Cells as a Therapy for Neurodegenerative Diseases

Kan

Melamed

Offen

2007

Handbook of Experimental Pharmacology

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Neurodegenerative diseases are characterized by a progressive degeneration of selective neural populations. This selective hallmark pathology and the lack of effective treatment modalities make these diseases appropriate candidates for cell therapy. Bone marrow-derived mesenchymal stem cells (MSCs) are self-renewing precursors that reside in the bone marrow and may further be exploited for autologous transplantation. Autologous transplantation of MSCs entirely circumvents the problem of immune rejection, does not cause the formation of teratomas, and raises very few ethical or political concerns. More than a few studies showed that transplantation of MSCs resulted in clinical improvement. However, the exact mechanisms responsible for the beneficial outcome have yet to be defined. Possible rationalizations include cell replacement, trophic factors delivery, and immunomodulation. Cell replacement theory is based on the idea that replacement of degenerated neural cells with alternative functioning cells induces long-lasting clinical improvement. It is reasoned that the transplanted cells survive, integrate into the endogenous neural network, and lead to functional improvement. Trophic factor delivery presents a more practical short-term approach. According to this approach, MSC effectiveness may be credited to the production of neurotrophic factors that support neuronal cell survival, induce endogenous cell proliferation, and promote nerve fiber regeneration at sites of injury. The third potential mechanism of action is supported by the recent reports claiming that neuroinflammatory mechanisms play an important role in the pathogenesis of neurodegenerative disorders. Thus, inhibiting chronic inflammatory stress might explain the beneficial effects induced by MSC transplantation. Here, we assemble evidence that supports each theory and review the latest studies that have placed MSC transplantation into the spotlight of biomedical research.

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Glucocorticoid receptor–nitric oxide crosstalk and vulnerability to experimental parkinsonism: pivotal role for glia–neuron interactions

Cited by 55 publications

References 132 publications

Estrogen anti-inflammatory activity in brain: A therapeutic opportunity for menopause and neurodegenerative diseases

Estrogen anti-inflammatory activity in brain: A therapeutic opportunity for menopause and neurodegenerative diseases

β-Funaltrexamine Inhibits Inducible Nitric-oxide Synthase Expression in Human Astroglial Cells

Autotransplantation of Bone Marrow-Derived Stem Cells as a Therapy for Neurodegenerative Diseases

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