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Feligioni M.,Laboratory of Pharmacology of Synaptic Plasticity | Nistico R.,University of Rome La Sapienza | Nistico R.,Laboratory of Experimental Neurology
NeuroMolecular Medicine | Year: 2013

Redox species are produced during the physiological cellular metabolism of a normal tissue. In turn, their presence is also attributed to pathological conditions including neurodegenerative diseases. Many are the molecular changes that occur during the unbalance of the redox homeostasis. Interestingly, posttranslational protein modifications (PTMs) play a remarkable role. In fact, several target proteins are modified in their activation, localization, aggregation, and expression after the cellular stress. Among PTMs, protein SUMOylation represents a very important molecular modification pathway during "oxidative stress". It has been reported that this ubiquitin-like modification is a fine sensor for redox species. Indeed, SUMOylation pathway efficiency is affected by the exposure to oxidative species in a different manner depending on the concentration and time of application. Thus, we here report updated evidence that states the role of SUMOylation in several pathological conditions, and we also outline the key involvement of c-Jun N-terminal kinase and small ubiquitin modifier pathway cross talk. © 2013 Springer Science+Business Media New York. Source

Scaccianoce S.,University of Rome La Sapienza | Caruso A.,University of Rome La Sapienza | Miele J.,University of Rome La Sapienza | Nistico R.,University of Rome La Sapienza | And 2 more authors.
Journal of Biological Regulators and Homeostatic Agents | Year: 2013

Anabolic androgenic steroids (AASs) are synthetic androgen-like compounds which are abused in sport communities despite their side effects. AAS abuse has been coupled with several medical complications, such as sterility, gynecomastia, and increased risk of cardiovascular and hepatic diseases. More recently, it has been observed that non-medical use of these steroids is frequently associated with changes in mood as well as cognitive deficits. Although the nature of this association is still largely unexplored, recent animal studies have shown the neurodegenerative potential of these compounds ranging from neurotrophin unbalance to increased neuronal susceptibility to apoptotic stimuli. Hence, exposure to AASs may result in a compromised brain, more susceptible, later in life, to the onset or progression of diseases not usually linked to drug abuse, especially neurodegenerative diseases. Copyright © by BIOLIFE, s.a.s. Source

Vezzani A.,Laboratory of Experimental Neurology
Expert Opinion on Drug Safety | Year: 2015

Introduction: In the epilepsy therapeutic arena, there is urgent need for developing novel antiepileptogenesis treatments that offer a way to prevent the onset or the progression of the disease. Such treatments are still lacking, and their development requires a deep understanding of the mechanisms underlying the disease pathogenesis, in order to target them using appropriate drugs with timely interventions.Areas covered: Preclinical research highlighted glial cells in seizure-prone areas as key contributors to neuronal circuit hyperexcitability resulting in seizures. Microglia and astrocytes activated by epileptogenic insults increase their synthesis and release of pro-inflammatory molecules, thus contributing to the generation of neuroinflammation. This is now considered an established hallmark of epileptogenic foci in various forms of pharmaco-resistant epilepsies. Studies done in experimental models of non-genetic forms of epilepsy demonstrated that specific inflammatory molecules are involved in seizures, cell loss and co-morbidities.Expert opinion: Emerging findings highlight that specific inflammatory molecules are potential targets for drug intervention for preventing or arresting epileptogenesis. These drugs, by interfering with mechanisms implicated in disease development, may represent disease-modifying treatments. Clinical translation of anti-inflammatory intervention may take advantage of drugs already used in clinical practice for peripheral or other CNS disorders with a pathogenic neuroinflammatory component. © 2015 Informa UK, Ltd. Source

Lefranc M.,Amiens University Hospital | Lefranc M.,French Institute of Health and Medical Research | Manto M.,Laboratory of Experimental Neurology | Merle P.,Amiens University Hospital | And 7 more authors.
Cerebellum | Year: 2014

Deep brain stimulation of the thalamus (and especially the ventral intermediate nucleus) does not significantly improve a drug-resistant, disabling cerebellar tremor. The dentato-rubro-olivary tract (Guillain-Mollaret triangle, including the red nucleus) is a subcortical loop that is critically involved in tremor genesis.We report the case of a 48-year-old female patient presenting with generalized cerebellar tremor caused by alcohol-related cerebellar degeneration. Resistance to pharmacological treatment and the severity of the symptoms prompted us to investigate the effects of bilateral deep brain stimulation of the red nucleus. Intra-operative microrecordings of the red nucleus revealed intense, irregular, tonic background activity but no rhythmic components that were synchronous with upper limb tremor. The postural component of the cerebellar tremor disappeared during insertion of the macro-electrodes and for a few minutes after stimulation, with no changes in the intentional (kinetic) component. Stimulation per se did not reduce postural or intentional tremor and was associated with dysautonomic symptoms (the voltage threshold for which was inversed related to the stimulation frequency). Our observations suggest that the red nucleus is (1) an important centre for the genesis of cerebellar tremor and thus (2) a possible target for drug-refractory tremor. Future research must determine how neuromodulation of the red nucleus can best be implemented in patients with cerebellar degeneration. © Springer Science+Business Media 2014. Source

Amantea D.,University of Calabria | Bagetta G.,University of Calabria | Tassorelli C.,University of Pavia | Mercuri N.B.,Laboratory of Experimental Neurology | Corasaniti M.T.,University of Catanzaro
Brain Research | Year: 2010

The proinflammatory cytokine interleukin(IL)-1β plays a crucial role in ischemic pathophysiology, since pharmacologic inhibition of its biological effects provides neuroprotection after stroke. However, there is evidence suggesting that under certain circumstances the cytokine may also exert beneficial functions on brain injury. We have investigated the regional and cellular expression of IL-1β after ischemia-reperfusion injury in the brain of rat, and correlated cytokine expression with the activation/recruitment of glial cells in the damaged tissue. By using a double immunofluorescence histochemical approach, we observed an increased cytokine immunoreactivity in the ischemic core, as early as 1 h after middle cerebral artery occlusion, in few activated OX-42-positive microglial cells and in perivascular GFAP-positive astrocytes, suggesting that the cytokine may participate in the early response of the neurovascular unit to reduced blood supply. After 2 h ischemia, followed by 2 h reperfusion, cytokine staining was evident in the astrocytes of the penumbra and in activated microglial cells of the ischemic core. Microglial activation increases with the progression of damage and, after 22 h reperfusion, OX-42-immunopositive cells were strongly labelled for IL-1β in the core and, even more intensely, in the penumbra. At this later stage, GFAP-positive cells, appearing hypertrophic and distributed in a ring-like pattern around the ischemic core, do no longer express IL-1β. Thus, a specific cellular and regional pattern of IL-1β expression characterises the progression of ischemia-reperfusion injury. Depending on the stage and intensity of the insult, the different cellular origin of the cytokine may suggest a distinct role of this neuroinflammatory mediator in ischemic pathophysiology. © 2009 Elsevier B.V. All rights reserved. Source

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