Papers by Roberto Coccurello
Social Science Research Network, 2019
HAL (Le Centre pour la Communication Scientifique Directe), 2005
HAL (Le Centre pour la Communication Scientifique Directe), 2005
British Journal of Pharmacology, Jan 13, 2022
Background and PurposeAmyotrophic lateral sclerosis (ALS), a neurodegenerative disease characteri... more Background and PurposeAmyotrophic lateral sclerosis (ALS), a neurodegenerative disease characterized by the degeneration of upper and lower motor neurons, progressive wasting and paralysis of voluntary muscles and is currently incurable. Although considered to be a pure motor neuron disease, increasing evidence indicates that the sole protection of motor neurons by a single targeted drug is not sufficient to improve the pathological phenotype. We therefore evaluated the therapeutic potential of the multi‐target drug used to treatment of coronary artery disease, trimetazidine, in SOD1G93Amice.Experimental ApproachAs a metabolic modulator, trimetazidine improves glucose metabolism. Furthermore, trimetazidine enhances mitochondrial metabolism and promotes nerve regeneration, exerting an anti‐inflammatory and antioxidant effect. We orally treated SOD1G93Amice with trimetazidine, solubilized in drinking water at a dose of 20 mg kg−1, from disease onset. We assessed the impact of trimetazidine on disease progression by studying metabolic parameters, grip strength and histological alterations in skeletal muscle, peripheral nerves and the spinal cord.Key ResultsTrimetazidine administration delays motor function decline, improves muscle performance and metabolism, and significantly extends overall survival of SOD1G93Amice (increased median survival of 16 days and 12.5 days for male and female respectively). Moreover, trimetazidine prevents the degeneration of neuromuscular junctions, attenuates motor neuron loss and reduces neuroinflammation in the spinal cord and in peripheral nerves.Conclusion and ImplicationsIn SOD1G93Amice, therapeutic effect of trimetazidine is underpinned by its action on mitochondrial function in skeletal muscle and spinal cord.
Zenodo (CERN European Organization for Nuclear Research), Jul 19, 2021
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
HAL (Le Centre pour la Communication Scientifique Directe), 2006
Workshop of the European-Behavioural-Pharmacology-Society on Neurodegeneration - Basic Mechanisms... more Workshop of the European-Behavioural-Pharmacology-Society on Neurodegeneration - Basic Mechanisms of Motor and Cognitive Dysfunctions, Cracow, POLAND, SEP 02-04, 2006International audienceno abstrac
HAL (Le Centre pour la Communication Scientifique Directe), 2006
Overactivation of excitatory amino acid receptors has been involved in several neurodegenerative ... more Overactivation of excitatory amino acid receptors has been involved in several neurodegenerative diseases. The present study aims at investigating the potential neuroprotective action of 2-methyl-6-(phenylethylnyl)-pyridine (MPEP), a selective non-competitive antagonist of metabotropic glutamate receptor subtype 5, and 2-amino-6-trifluoro methoxy-benzothiole (riluzole), a Na ؉ channel blocker exhibiting anti-glutamatergic properties, on the ibotenateinduced damage to the rat medial prefrontal cortex. The neuroprotective efficacy of these compounds was assessed on the recovery from behavioral deficits induced by prefrontal cortical excitotoxic lesions in a reaction time task. MPEP (3, 10 or 30 mg/kg) or riluzole (2, 4 or 8 mg/kg) was administered i.p. 30 min before and after medial prefrontal cortex lesions. As previously found, lesions to the medial prefrontal cortex significantly altered the motor preparatory processes involved in the reaction time task. These deficits were prevented by MPEP 3 mg/kg and riluzole 2 mg/kg while higher doses of either compound were ineffective. Furthermore, the neuronspecific nuclear protein immunostaining of the lesioned cortical area in animals treated with the efficient dose of either compound revealed that MPEP reduced the volume of the lesion whereas riluzole reversed the decrease of neuronal density within the lesioned area. Altogether, these results suggest a neuroprotective action of MPEP as well as riluzole at both behavioral and cellular levels on excitatory amino acid-induced toxicity.
Frontiers in Cell and Developmental Biology, 2021
The dentate gyrus of the hippocampus and the subventricular zone are neurogenic niches where neur... more The dentate gyrus of the hippocampus and the subventricular zone are neurogenic niches where neural stem and progenitor cells replicate throughout life to generate new neurons. The Btg1 gene maintains the stem cells of the neurogenic niches in quiescence. The deletion of Btg1 leads to an early transient increase of stem/progenitor cells division, followed, however, by a decrease during adulthood of their proliferative capability, accompanied by apoptosis. Since a physiological decrease of neurogenesis occurs during aging, the Btg1 knockout mouse may represent a model of neural aging. We have previously observed that the defective neurogenesis of the Btg1 knockout model is rescued by the powerful neurogenic stimulus of physical exercise (running). To identify genes responsible for stem and progenitor cells maintenance, we sought here to find genes underlying this premature neural aging, and whose deregulated expression could be rescued by running. Through RNA sequencing we analyzed t...
Brain Communications, 2020
Clinical and neuropathological studies have shown that tau pathology better correlates with the s... more Clinical and neuropathological studies have shown that tau pathology better correlates with the severity of dementia than amyloid plaque burden, making tau an attractive target for the cure of Alzheimer’s disease. We have explored whether passive immunization with the 12A12 monoclonal antibody (26–36aa of tau protein) could improve the Alzheimer’s disease phenotype of two well-established mouse models, Tg2576 and 3xTg mice. 12A12 is a cleavage-specific monoclonal antibody which selectively binds the pathologically relevant neurotoxic NH226-230 fragment (i.e. NH2htau) of tau protein without cross-reacting with its full-length physiological form(s). We found out that intravenous administration of 12A12 monoclonal antibody into symptomatic (6 months old) animals: (i) reaches the hippocampus in its biologically active (antigen-binding competent) form and successfully neutralizes its target; (ii) reduces both pathological tau and amyloid precursor protein/amyloidβ metabolisms involved in...
International Journal of Molecular Sciences
Neuropathic pain (NeuP) is still an intractable form of highly debilitating chronic pain, resulti... more Neuropathic pain (NeuP) is still an intractable form of highly debilitating chronic pain, resulting from a lesion or disease of the somatosensory nervous system [...]
International Journal of Molecular Sciences, 2019
There is robust evidence indicating that enhancing the endocannabinoid (eCB) tone has therapeutic... more There is robust evidence indicating that enhancing the endocannabinoid (eCB) tone has therapeutic potential in several brain disorders. The inhibition of eCBs degradation by fatty acid amide hydrolase (FAAH) blockade, is the best-known option to increase N-acyl-ethanolamines-(NAEs)-mediated signaling. Here, we investigated the hypothesis that intranasal delivery is an effective route for different FAAH inhibitors, such as URB597 and PF-04457845. URB597 and PF-04457845 were subchronically administered in C57BL/6 male mice every other day for 20 days for overall 10 drug treatment, and compared for their ability to inhibit FAAH activity by the way of three different routes of administration: intranasal (i.n.), intraperitoneal (i.p.) and oral (p.o.). Lastly, we compared the efficacy of the three routes in terms of URB597-induced increase of NAEs levels in liver and in different brain areas. Results: We show that PF-04457845 potently inhibits FAAH regardless the route selected, and that ...
International Journal of Molecular Sciences
The present editorial intends to comment on the contributions published in the second edition of ... more The present editorial intends to comment on the contributions published in the second edition of the Special Issue (SI) “The Multiple Mechanisms Underlying Neuropathic Pain” [...]
Frontiers in Psychiatry
The occurrence of neuropsychiatric symptoms in the elderly is viewed as an early sign of subseque... more The occurrence of neuropsychiatric symptoms in the elderly is viewed as an early sign of subsequent cognitive deterioration and conversion from mild cognitive impairment to Alzheimer’s disease. The prognosis in terms of both the severity and progression of clinical dementia is generally aggravated by the comorbidity of neuropsychiatric symptoms and decline in cognitive function. Undeniably, aging and in particular unhealthy aging, is a silent “engine of neuropathology” over which multiple changes take place, including drastic alterations of the gut microbial ecosystem. This narrative review evaluates the role of gut microbiota changes as a possible unifying concept through which the comorbidity of neuropsychiatric symptoms and Alzheimer’s disease can be considered. However, since the heterogeneity of neuropsychiatric symptoms, it is improbable to describe the same type of alterations in the bacteria population observed in patients with Alzheimer’s disease, as well as it is improbabl...
International Journal of Molecular Sciences, Nov 22, 2022
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Behavioural Pharmacology, 2003
10th Biennial Meeting of the European-Behavioural-Pharmacology-Society, ANTWERP, BELGIUM, SEP 06-... more 10th Biennial Meeting of the European-Behavioural-Pharmacology-Society, ANTWERP, BELGIUM, SEP 06-09, 2003International audienceno abstrac
For many years now the world's scientific literature has been perfused with articles on the thera... more For many years now the world's scientific literature has been perfused with articles on the therapeutic potential of natural products, the vast majority of which have herbal origins, as in the case of free radical-induced diseases. What is often overlooked is the effort of researchers who take into consideration the preclinical and clinical evaluation of these herbal products, in order to demonstrate the therapeutic efficacy and safety. The first critical issue to be addressed in the early stages of the preclinical studies is related to pharmacokinetics, which is sometimes not very favorable, of some of these products, which limits the bioavailability after oral intake. In this regard, it is worthy underlining how it is often unethical to propose the therapeutic efficacy of a compound on the basis of preclinical results obtained with far higher concentrations to those which, hopefully, could be achieved in organs and tissues of subjects taking these products by mouth. The most widely used approach to overcome the problem related to the low bioavailability involves the complexation of the active ingredients of herbal products with non-toxic carriers that facilitate the absorption and distribution. Even the induction or inhibition of drug metabolizing enzymes by herbal products, and the consequent variations of plasma concentrations of co-administered drugs, are phenomena to be carefully evaluated as they can give rise to side-effects. This risk is even greater when considering that people lack the perception of the risk arising from an over use of herbal products that, by their very nature, are considered risk-free.
It has been estimated that more than half of all epilepsies have some genetic basis and over the ... more It has been estimated that more than half of all epilepsies have some genetic basis and over the pastdecade important progresses have been made in the understanding of the genetic causes of many ofthese epilepsies. Single gene defects in ion channels or neurotransmitter receptors are associated withsome inherited forms of epilepsy [1-6]. In addition, genetic discoveries in the field of infantile epilepsy syndromes have highlighted the possible different aetiologies other than channelopathies can result in epilepsy [7]. The importance of genetic testing has been highlighted inclinical contexts where the identification of a specific cause may clarify the prognosis, identify the bestavailable treatment, and define the risk of recurrence for current and future family members and avoidinvasive and or prolonged diagnostic processes [8]. Moreover, genetic testing allows understanding therole of the mutation and its relationship with the phenotype, thus helping in the definition of points o...
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Papers by Roberto Coccurello