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Parkinson Disease: HELP
Articles from University of Cagliari
Based on 114 articles published since 2010
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These are the 114 published articles about Parkinson Disease that originated from University of Cagliari during 2010-2020.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5
1 Editorial The sweet road to Parkinson's disease. 2019

Renaud, Justine / Simola, Nicola / Martinoli, Maria-Grazia. ·Cellular Neurobiology, Department of Medical Biology, Université du Québec, Trois-Rivières, Canada. · Department of Biomedical Sciences, Università di Cagliari, Cagliari, Italy. · National Institute of Neuroscience, Università di Cagliari, Cagliari, Italy. · Department of Psychiatry and Neuroscience, Université Laval and CHU Research Center, Québec, Canada. ·Aging (Albany NY) · Pubmed #30708352.

ABSTRACT: -- No abstract --

2 Editorial Dyskinesia in Parkinson's disease: a clinical complication and an open scientific question. 2018

Carta, Manolo / Hirsch, Etienne. ·Department of Biomedical Sciences, University of Cagliari, Cittadella Universitaria SP 8, 09042, Monserrato, Italy. manolocarta@unica.it. · Inserm U 1127, CNRS UMR 7225, Sorbonne Universités, Institut du Cerveau et de la Moelle épinière, ICM, 75013, Paris, France. ·J Neural Transm (Vienna) · Pubmed #30014356.

ABSTRACT: -- No abstract --

3 Review Modifiable risk and protective factors in disease development, progression and clinical subtypes of Parkinson's disease: What do prospective studies suggest? 2020

Belvisi, Daniele / Pellicciari, Roberta / Fabbrini, Giovanni / Tinazzi, Michele / Berardelli, Alfredo / Defazio, Giovanni. ·IRCCS Neuromed, via Atinense 18, 86077 Pozzilli, IS, Italy. · Department of Basic Medical Sciences, Neuroscience and Sense Organs, "Aldo Moro", University of Bari, Bari, Italy. · IRCCS Neuromed, via Atinense 18, 86077 Pozzilli, IS, Italy; Department of Human Neurosciences, Sapienza University of Rome, Viale dell' Università 30, 00185 Rome, Italy. · Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Via Casorati 43, 37131 Verona, Italy. · IRCCS Neuromed, via Atinense 18, 86077 Pozzilli, IS, Italy; Department of Human Neurosciences, Sapienza University of Rome, Viale dell' Università 30, 00185 Rome, Italy. Electronic address: alfredo.berardelli@uniroma1.it. · Department of Medical Sciences and Public Health, University of Cagliari, SS 554 bivio Sestu, 09042 Monserrato, CA, Italy. ·Neurobiol Dis · Pubmed #31706021.

ABSTRACT: Parkinson's disease (PD) is a neurodegenerative disorder whose pathogenesis depends on a combination of genetic and environmental factors. The aim of the present review was to provide an updated description of the findings emerging from prospective longitudinal cohort studies on the possible risk/protective factors underlying the development, progression and clinical subtypes of PD. We reviewed all the environmental, lifestyle, dietary, comorbid and pharmacological factors that have been investigated as possible modifiable protective/risk factors for PD by longitudinal studies. Only a few factors have the epidemiological evidence and the biological plausibility to be considered risk (pesticides, dairy products, β2-adrenoreceptor antagonists) or protective (smoking, caffeine and tea intake, physical activity, gout, vitamin E intake, non-steroidal anti-inflammatory drugs and β2-adrenoreceptor agonists) factors for PD. Caffeine intake and physical activity also seem to slow down the progression of the disease, thus representing good candidates for primary prevention and disease modifying strategies in PD. Possible modifiable risk factors of PD subtypes is almost unknown and this might depend on the uncertain biological and neuropathological reliability of clinical subtypes. The results of the present review suggest that only eleven risk/protective factors may be associated with the risk of PD. It may be possible to target some of these factors for preventive interventions aimed at reducing the risk of developing and the rate of progression of PD.

4 Review Sleep in Parkinson's Disease with Impulse Control Disorder. 2018

Figorilli, Michela / Congiu, Patrizia / Lecca, Rosa / Gioi, Gioia / Frau, Roberto / Puligheddu, Monica. ·Sleep Disorders Center, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy. · Department of Biomedical Sciences, Division of Neuroscience and Clinical Pharmacology, University of Cagliari, Cagliari, Italy. · Sleep Disorders Center, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy. puligheddu@unica.it. · Sleep Disorder Centre, Department of Public Health and Clinical and Molecular Medicine, University of Cagliari, ss 554 bivio Sestu 09042 Monserrato, Cagliari, Italy. puligheddu@unica.it. ·Curr Neurol Neurosci Rep · Pubmed #30099617.

ABSTRACT: PURPOSE OF REVIEW: This paper aims to explore the relationship between impulse-control disorders (ICDs) and sleep problems in patients with Parkinson's disease (PD) among scientific literature. RECENT FINDINGS: Previously published results are controversial and sometimes inconclusive. ICDs and sleep disruption represent important non-motor features of Parkinson's disease, responsible for reducing quality of life and increasing burden of disease. The relationship between sleep problems and ICDs is complex and bidirectional. Indeed, sleep disturbances and fragmentation may play a crucial role in increasing susceptibility to impulsive behavior and may represent a risk factor for developing ICDs in PD patients. Moreover, REM sleep behavior disorder (RBD) and restless legs syndrome (RLS) have been indicated as independent risk factors for ICDs in PD patients. On the other hand, also ICDs may lead to sleep restriction and fragmentation, suggesting a bidirectional relationship. The association between sleep problems and ICDs in PD is far from being completely understood. Further studies are needed to confirm the nature of this relationship and its pathophysiology.

5 Review Pain in Parkinson's disease: facts and uncertainties. 2018

Antonini, A / Tinazzi, M / Abbruzzese, G / Berardelli, A / Chaudhuri, K R / Defazio, G / Ferreira, J / Martinez-Martin, P / Trenkwalder, C / Rascol, O. ·University of Padua, Padua. · University of Verona, Verona. · University of Genoa, Genoa. · University of Rome, Rome. · IRCCS NEUROMED, Isernia, Italy. · Kings College London, London, UK. · University of Cagliari, Cagliari, Italy. · Hospital de Santa Maria, Lisbon, Portugal. · National Center of Epidemiology and CIBERNED, Madrid, Spain. · University Medical Center Goettingen, Goettingen, Germany. · Université de Toulouse, Toulouse, France. ·Eur J Neurol · Pubmed #29520899.

ABSTRACT: Pain is one of the most common and troublesome non-motor symptoms of Parkinson's disease (PD). It can appear at any time during the disease and is often present before diagnosis. However, there is little or no consensus on its definition. An expert group of clinicians with relevant research experience met to review the existing evidence and to identify gaps in our understanding leading towards AUTHOR: 'understanding towards' has been changed to 'understanding leading towards'. Please check and confirm that this is appropriate an optimized therapy of pain in PD. Key findings from epidemiologic, neurophysiologic, neuroimaging and clinical studies are reviewed. In each case, the evidence base is limited by wide variations in the definitions of pain applied, study methodologies and populations evaluated. Disease-related and medical conditions trigger spontaneous pain in patients with PD, which is then abnormally processed and results in painful manifestations in specific body parts. Dopaminergic medications, such as rotigotine, as well as opiate analgesics, such as oxycodone, have shown positive results but future studies with more detailed pain characterization at inclusion are warranted.

6 Review The serotonergic system in L-DOPA-induced dyskinesia: pre-clinical evidence and clinical perspective. 2018

Carta, Manolo / Björklund, Anders. ·Department of Biomedical Sciences, Section of Physiology, University of Cagliari, Cittadella Universitaria, SS554, Km 4.5, 09042, Monserrato, Italy. manolocarta@unica.it. · Division of Neurobiology, Department of Experimental Medical Science, Wallenberg Neuroscience Center, Lund University, 221 84, Lund, Sweden. ·J Neural Transm (Vienna) · Pubmed #29480391.

ABSTRACT: During the last decade, the serotonergic system has emerged as a key player in the appearance of L-DOPA-induced dyskinesia in animal models of Parkinson's disease. Clinical investigations, based on imaging and postmortem analyses, suggest that the serotonin neurons are also involved in the etiology of this complication of long-term L-DOPA treatment in parkinsonian patients. These findings have stimulated efforts to develop new therapies using drugs targeting the malfunctioning serotonin neurons. In this review, we summarize the experimental and clinical data obtained so far and discuss the prospects for further development of this therapeutic strategy.

7 Review Role of adenosine A 2018

Pinna, Annalisa / Serra, Marcello / Morelli, Micaela / Simola, Nicola. ·Neuroscience Institute - Cagliari, National Research Council of Italy (CNR), Building A, Cittadella Universitaria di Monserrato, 09042, Monserrato (CA), Italy. apinna@unica.it. · Department of Biomedical Sciences, Section of Neuropsychopharmacology, University of Cagliari, Cagliari, Italy. · Neuroscience Institute - Cagliari, National Research Council of Italy (CNR), Building A, Cittadella Universitaria di Monserrato, 09042, Monserrato (CA), Italy. · National Institute of Neuroscience (INN), University of Cagliari, Cagliari, Italy. ·J Neural Transm (Vienna) · Pubmed #29396609.

ABSTRACT: Adenosine is an endogenous purine nucleoside that regulates several physiological functions, at the central and peripheral levels. Besides, adenosine has emerged as a major player in the regulation of motor behavior. In fact, adenosine receptors of the A

8 Review Animal models of L-DOPA-induced dyskinesia: the 6-OHDA-lesioned rat and mouse. 2018

Tronci, Elisabetta / Francardo, Veronica. ·Department of Biomedical Sciences, Section of Physiology, University of Cagliari, Cittadella Universitaria, SS554 Km 4.5, 09042, Monserrato, Italy. elitronci@yahoo.it. · Basal Ganglia Pathophysiology Unit, Department of Experimental Medical Science, Lund University, Lund, Sweden. ·J Neural Transm (Vienna) · Pubmed #29242978.

ABSTRACT: Appearance of L-DOPA-induced dyskinesia (LID) represents a major limitation in the pharmacological therapy with the dopamine precursor L-DOPA. Indeed, the vast majority of parkinsonian patients develop dyskinesia within 9-10 years of L-DOPA oral administration. This makes the discovery of new therapeutic strategies an important need. In the last decades, several animal models of Parkinson's disease (PD) have been developed, to both study mechanisms underlying PD pathology and treatment-induced side effects (i.e., LID) and to screen for new potential anti-parkinsonian and anti-dyskinetic treatments. Among all the models developed, the 6-OHDA-lesioned rodents represent the models of choice to mimic PD motor symptoms and LID, thanks to their reproducibility and translational value. Under L-DOPA treatment, rodents sustaining 6-OHDA lesions develop abnormal involuntary movements with dystonic and hyperkinetic features, resembling what seen in dyskinetic PD patients. These models have been extensively validated by the evidence that dyskinetic behaviors are alleviated by compounds reducing dyskinesia in patients and non-human primate models of PD. This article will focus on the translational value of the 6-OHDA rodent models of LID, highlighting their main features, advantages and disadvantages in preclinical research.

9 Review Nordic Walking for the Management of People With Parkinson Disease: A Systematic Review. 2017

Cugusi, Lucia / Manca, Andrea / Dragone, Daniele / Deriu, Franca / Solla, Paolo / Secci, Claudio / Monticone, Marco / Mercuro, Giuseppe. ·Department of Medical Sciences and Public Health, University of Cagliari, SS 554, Km 4.500, 09042 Monserrato, Cagliari, Italy(∗). Electronic address: lucia.cugusi@unica.it. · Department of Biomedical Sciences, University of Sassari, Sassari, Italy(†). · Department of Biomedical Sciences, University of Sassari, Sassari, Italy(‡). · Department of Biomedical Sciences, University of Sassari, Sassari, Italy(§). · Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy(¶). · Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy(#). · Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy(∗∗). · Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy(††). ·PM R · Pubmed #28694221.

ABSTRACT: BACKGROUND: It is well known that physical exercise is the main therapeutic element of rehabilitation programs for people with Parkinson disease (PD). As traditional forms of exercise can guarantee significant health benefits, the emergence of nonconventional physical activities, such as Nordic walking (NW), may add positive effects. OBJECTIVE: To appraise the available evidence on the main effects of NW in the rehabilitation programs for people with PD and to propose a design for upcoming research that might improve the uniformity of future trials. STUDY DESIGN: Systematic review. LITERATURE SURVEY: A literature search of 5 established databases (PubMed, MEDLINE, Scopus, Web of Science, and Cochrane) was conducted. METHODOLOGY: Any relevant randomized controlled trials pertinent to NW in PD published in English from inception to February 2017 were included. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed, and the methodologic quality of each study was assessed by the Physiotherapy Evidence Database scale. DATA SYNTHESIS: Sixty-six studies were retrieved, and 6 randomized controlled trials (221 subjects) were entered into the qualitative synthesis. Overall, these studies portrayed NW as feasible and likely to be effective in improving the functional and clinical outcomes of people with PD. When we compared NW with other exercise-based interventions, such as treadmill training, free walking, a program of standardized whole-body movements with maximal amplitude (Lee Silverman Voice Treatment BIG training), or a home-based exercise program, the findings proved controversial. CONCLUSIONS: High heterogeneity and methodologic discrepancies among the studies prevent us from drawing firm conclusions on the effectiveness of NW in comparison with other exercise-based interventions currently used by people with PD. Further investigations with a common design are necessary to verify whether NW may be included within conventional rehabilitation programs commonly recommended to people with PD. LEVEL OF EVIDENCE: II.

10 Review Subthalamic nucleus stimulation and gait in Parkinson's Disease: a not always fruitful relationship. 2017

Cossu, Giovanni / Pau, Massimiliano. ·"G. Brotzu" General Hospital, Department of Neurology, Cagliari, Italy. · Department of Mechanical, Chemical and Materials Engineering, University of Cagliari, Cagliari, Italy. Electronic address: massimiliano.pau@dimcm.unica.it. ·Gait Posture · Pubmed #27915226.

ABSTRACT: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) provides efficient treatment for the alleviation of motor signs in patients with advanced Parkinson's disease (PD), but its specific effects on gait is sometimes less successful as it may even lead to an aggravation of freezing of gait. To better understand when axial symptoms can be expected to improve and when they may worsen or be resistant to STN-DBS, we propose here a narrative review that considers the recent literature evidences based on instrumental gait analysis data. Our aim is to report about the efficacy of STN-DBS on PD gait, analyzing the clinical and procedural factors involved, and discussing the strategies for optimizing such effectiveness in patients with advanced PD.

11 Review l-DOPA-induced dyskinesia and neuroinflammation: do microglia and astrocytes play a role? 2017

Carta, Anna R / Mulas, Giovanna / Bortolanza, Mariza / Duarte, Terence / Pillai, Elisabetta / Fisone, Gilberto / Vozari, Rita Raisman / Del-Bel, Elaine. ·Department of Biomedical Sciences, University of Cagliari, Cittadella Universitaria di Monserrato, S.P. N. 8, 09042, Monserrato, Cagliari, Italy. · School of Odontology of Ribeirão Preto, Department of Morphology, Physiology and Basic Pathology, University of São Paulo (USP), Av. Café S/N, 14040-904, Ribeirão Preto, SP, Brazil. · USP, Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), São Paulo, Brazil. · Department of Neuroscience, Karolinska Institutet, Retzius väg 8, 17177, Stockholm, Sweden. · INSERM U 1127, CNRS UMR 7225, UPMC Univ Paris 06, UMR S 1127, Institut Du Cerveau et de La Moelle Epiniére, ICM, Paris, France. ·Eur J Neurosci · Pubmed #27859864.

ABSTRACT: In Parkinson's disease (PD), l-DOPA therapy leads to the emergence of motor complications including l-DOPA-induced dyskinesia (LID). LID relies on a sequence of pre- and postsynaptic neuronal events, leading to abnormal corticostriatal neurotransmission and maladaptive changes in striatal projection neurons. In recent years, additional non-neuronal mechanisms have been proposed to contribute to LID. Among these mechanisms, considerable attention has been focused on l-DOPA-induced inflammatory responses. Microglia and astrocytes are the main actors in neuroinflammatory responses, and their double role at the interface between immune and neurophysiological responses is starting to be elucidated. Both microglia and astrocytes express a multitude of neurotransmitter receptors and via the release of several soluble molecules modulate synaptic function in neuronal networks. Here we review preclinical and clinical evidence of glial overactivation by l-DOPA, supporting a role of microglia and astrocytes in the development of LID. We propose that in PD, chronically and abnormally activated microglia and astrocytes lead to an aberrant neuron-glia communication, which affect synaptic activity and neuroplasticity contributing to the development of LID.

12 Review Capgras syndrome in Parkinson's disease: two new cases and literature review. 2017

Cannas, Antonino / Meloni, Mario / Mascia, Marcello Mario / Solla, Paolo / Cocco, Luigi / Muroni, Antonella / Floris, Gianluca / Di Stefano, Francesca / Marrosu, Francesco. ·Department of Neurology, Movement Disorders Center, Policlinico Universitario Monserrato, University of Cagliari, SS 554 Bivio per Sestu, Monserrato, 09042, Cagliari, Italy. · Department of Neurology, Movement Disorders Center, Policlinico Universitario Monserrato, University of Cagliari, SS 554 Bivio per Sestu, Monserrato, 09042, Cagliari, Italy. mario.meloni@hotmail.it. ·Neurol Sci · Pubmed #27848117.

ABSTRACT: The Capgras syndrome (CS) is a rare psychiatric disorder. CS is classified as a delusional misidentification syndrome. Initially, CS was described in paranoid schizophrenia and schizoaffective disorders. CS has also been reported in neurodegenerative diseases such as Alzheimer's disease and Lewy body dementia. To date, there are very few descriptions of the occurrence of CS in idiopathic Parkinson's disease (PD), with or without dementia. Considering the recent observation of two new cases in PD patients, a systematic overview of the literature published between 1976 and 2016 reporting CS in PD was conducted. The purpose of this article is to examine the phenomenon in people with PD with and without dementia, the psychopathologic context in which it happened, the role played by the dopaminergic medications and to define useful therapeutic strategies. Our CS cases occurred in two elderly patients with advanced PD and cognitive impairment, respectively, after an acute stressor event and after an increase of the total daily dose of levodopa. In light of our observations and the cases reported in the literature, we argue that CS is an acute or subacute psychotic disorder occurring mostly in PD with dementia. Besides, the increase in brain dopamine levels induced by acute stressful events and/or dopamine-enhancing medications should be considered as a possible causal mechanism of CS in patients with advanced stages of PD and cognitive decline.

13 Review Microglial phenotypes in Parkinson's disease and animal models of the disease. 2017

Joers, Valerie / Tansey, Malú G / Mulas, Giovanna / Carta, Anna R. ·Department of Physiology, Emory University, Atlanta, GA, United States; Yerkes National Primate Research Center, Emory University, Atlanta, GA, United States. · Department of Physiology, Emory University, Atlanta, GA, United States. Electronic address: malu.tansey@emory.edu. · Department of Biomedical Sciences, University of Cagliari, Italy. · Department of Biomedical Sciences, University of Cagliari, Italy. Electronic address: acarta@unica.it. ·Prog Neurobiol · Pubmed #27107797.

ABSTRACT: Over the last decade the important concept has emerged that microglia, similar to other tissue macrophages, assume different phenotypes and serve several effector functions, generating the theory that activated microglia can be organized by their pro-inflammatory or anti-inflammatory and repairing functions. Importantly, microglia exist in a heterogenous population and their phenotypes are not permanently polarized into two categories; they exist along a continuum where they acquire different profiles based on their local environment. In Parkinson's disease (PD), neuroinflammation and microglia activation are considered neuropathological hallmarks, however their precise role in relation to disease progression is not clear, yet represent a critical challenge in the search of disease-modifying strategies. This review will critically address current knowledge on the activation states of microglia as well as microglial phenotypes found in PD and in animal models of PD, focusing on the expression of surface molecules as well as pro-inflammatory and anti-inflammatory cytokine production during the disease process. While human studies have reported an elevation of both pro- or anti-inflammatory markers in the serum and CSF of PD patients, animal models have provided insights on dynamic changes of microglia phenotypes in relation to disease progression especially prior to the development of motor deficits. We also review recent evidence of malfunction at multiple steps of NFκB signaling that may have a causal interrelationship with pathological microglia activation in animal models of PD. Finally, we discuss the immune-modifying strategies that have been explored regarding mechanisms of chronic microglial activation.

14 Review Paraphilias and paraphilic disorders in Parkinson's disease: A systematic review of the literature. 2015

Solla, Paolo / Bortolato, Marco / Cannas, Antonino / Mulas, Cesare Salvatore / Marrosu, Francesco. ·Movement Disorders Center, Department of Neurology, Institute of Neurology, University of Cagliari, Cagliari, Italy. ·Mov Disord · Pubmed #25759330.

ABSTRACT: Paraphilias are intense urges or behaviors involving non-normative sexual interests. The newly approved diagnostic criteria in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) have established that, although paraphilias should not be regarded as inherently pathological, they ought to be qualified as paraphilic disorders if resulting in distress, impairment, or harm to the affected individual or others. Recent evidence documents that both phenomena can emerge as relatively uncommon iatrogenic consequences in Parkinson's disease (PD) patients. To outline the clinical characteristics of paraphilias and paraphilic disorders in PD patients, we summarized the available evidence on these phenomena. The review encompasses all studies on paraphilias in PD patients identified by a search on the Pubmed and Scopus online databases through May 2014. Twenty-two case reports on a total of 31 PD patients with paraphilias or paraphilic disorders were identified. These phenomena were typically associated with dopaminomimetic treatment (with a mean levodopa-equivalent daily dose of 1,303 ± 823 mg/d) in male patients with motor complications, young age at PD onset, and long disease duration. Paraphilias were highly concomitant with impulse-control disorders or dopamine dysregulation syndrome. Although evidence on paraphilias and paraphilic disorders in PD patients remains anecdotal, available data point to these phenomena as likely sequelae of high-dose dopaminomimetic treatment. Accordingly, the intensity of paraphilic urges is typically attenuated by the reduction of dopaminomimetic doses, sometimes in association with atypical antipsychotics. Failure to recognize paraphilic disorders may significantly impair the relational functioning of the affected PD patients. Practitioners should routinely inquire about paraphilias during their clinical assessment of PD patients.

15 Review Thiazolidinediones under preclinical and early clinical development for the treatment of Parkinson's disease. 2015

Carta, Anna R / Simuni, Tanya. ·University of Cagliari, Department of Biomedical Sciences , via Ospedale 72, 09124, Cagliari , Italy +39 0706758662 ; +39 0706758665 ; acarta@unica.it. ·Expert Opin Investig Drugs · Pubmed #25227476.

ABSTRACT: INTRODUCTION: Current treatment of Parkinson's disease (PD) is limited to symptomatic dopaminergic therapy, while no interventions have been shown to slow down disease progression. AREAS COVERED: The following article highlights a group of PPAR-γ agonists called thiazolidinediones (TZDs), which are currently being tested for a putative disease-modifying benefit in PD, using pioglitazone as a prototypic compound. PPAR-γ is highly expressed in neurons of the substantia nigra and CNS immune cells. Preclinical data in rodent and primate support an effect of TZDs in preventing and/or arresting neurodegeneration and development of motor symptoms. Although no data on the neuroprotective effect of TZDs is currently available, a clinical trial is ongoing where the primary objective is to assess pioglitazone's impact on the progression of PD. The trial is also evaluating the drug's safety concerns. EXPERT OPINION: The efficacy data from clinical trials must be carefully weighed against the safety concerns. However, given the solid preclinical data, and since the safety data are not yet fully conclusive and limited to the diabetic population, PPAR-γ research in PD can continue with caution. Ideally, drug discovery and development efforts will lead to the identification of new compounds with reduced risk of peripheral side effects.

16 Review Serotonin System Implication in l-DOPA-Induced Dyskinesia: From Animal Models to Clinical Investigations. 2014

Carta, Manolo / Tronci, Elisabetta. ·Section of Physiology, Department of Biomedical Sciences, University of Cagliari , Monserrato , Italy. ·Front Neurol · Pubmed #24904522.

ABSTRACT: In the recent years, the serotonin system has emerged as a key player in the induction of l-DOPA-induced dyskinesia (LID) in animal models of Parkinson's disease. In fact, serotonin neurons possess the enzymatic machinery able to convert exogenous l-DOPA to dopamine (DA), and mediate its vesicular storage and release. However, serotonin neurons lack a feedback control mechanism able to regulate synaptic DA levels. While in a situation of partial DA depletion spared DA terminals can buffer DA released from serotonin neurons, the progression of DA neuron degeneration impairs this protective mechanism, causing swings in synaptic DA levels and pulsatile stimulation of post-synaptic DA receptors. In line with this view, removal of serotonin neurons by selective toxin, or pharmacological silencing of their activity, produced complete suppression of LID in animal models of Parkinson's disease. In this article, we will revise the experimental evidence pointing to the important role of serotonin neurons in dyskinesia, and we will discuss the clinical implications.

17 Review Adenosine A2A receptor antagonists in Parkinson's disease: progress in clinical trials from the newly approved istradefylline to drugs in early development and those already discontinued. 2014

Pinna, Annalisa. ·National Research Council of Italy (CNR), Neuroscience Institute-Cagliari, National Research Council of Italy (CNR), Via Ospedale, 72, 09124, Cagliari, Italy, apinna@unica.it. ·CNS Drugs · Pubmed #24687255.

ABSTRACT: Neurotransmitters other than dopamine, such as norepinephrine, 5-hydroxytryptamine, glutamate, adenosine and acetylcholine, are involved in Parkinson's disease (PD) and contribute to its symptomatology. Thus, the progress of non-dopaminergic therapies for PD has attracted much interest in recent years. Among new classes of drugs, adenosine A2A antagonists have emerged as promising candidates. The development of new highly selective adenosine A2A receptor antagonists, and their encouraging anti-parkinsonian responses in animal models of PD, has provided a rationale for clinical trials to evaluate the therapeutic potential and the safety of these agents in patients with PD. To date, the clinical research regarding A2A antagonists and their potential utilization in PD therapy continues to evolve between drugs just or previously discontinued (preladenant and vipadenant), new derivatives in development (tozadenant, PBF-509, ST1535, ST4206 and V81444) and the relatively old drug istradefylline, which has finally been licensed as an anti-parkinsonian drug in Japan. All these compounds have been shown to have a good safety profile and be well tolerated. Moreover, results from phase II and III trials also demonstrate that A2A antagonists are effective in reducing off-time, without worsening troublesome dyskinesia, and in increasing on-time with a mild increase of non-troublesome dyskinesia, in patients at an advanced stage of PD treated with L-DOPA. In addition, early findings suggest that A2A antagonists might also be efficacious as monotherapy in patients at an early stage of PD. This review summarizes pharmacological and clinical data available on istradefylline, tozadenant, PBF-509, ST1535, ST4206, V81444, preladenant and vipadenant.

18 Review Role of movement in long-term basal ganglia changes: implications for abnormal motor responses. 2013

Simola, Nicola / Morelli, Micaela / Frazzitta, Giuseppe / Frau, Lucia. ·1Section of Neuropsychopharmacology, Department of Biomedical Sciences, University of Cagliari Cagliari, Italy. ·Front Comput Neurosci · Pubmed #24167489.

ABSTRACT: Abnormal involuntary movements (AIMs) and dyskinesias elicited by drugs that stimulate dopamine receptors in the basal ganglia are a major issue in the management of Parkinson's disease (PD). Preclinical studies in dopamine-denervated animals have contributed to the modeling of these abnormal movements, but the precise neurochemical and functional mechanisms underlying these untoward effects are still elusive. It has recently been suggested that the performance of movement may itself promote the later emergence of drug-induced motor complications, by favoring the generation of aberrant motor memories in the dopamine-denervated basal ganglia. Our recent results from hemiparkinsonian rats subjected to the priming model of dopaminergic stimulation are in agreement with this. These results demonstrate that early performance of movement is crucial for the manifestation of sensitized rotational behavior, indicative of an abnormal motor response, and neurochemical modifications in selected striatal neurons following a dopaminergic challenge. Building on this evidence, this paper discusses the possible role of movement performance in drug-induced motor complications, with a look at the implications for PD management.

19 Review PPAR-γ: therapeutic prospects in Parkinson's disease. 2013

Carta, Anna R. ·Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy. acarta@unica.it ·Curr Drug Targets · Pubmed #23469878.

ABSTRACT: Parkinson's disease (PD) is amongst the most frequent neurodegenerative disorders, the main pathologic hallmark of which is the degeneration of the substantia nigra pars compacta. Damage to multiple cellular components, such as mitochondrial dysfunction, oxidative stress, neuroinflammation, and proteasomal dysfunction, contribute to the progression of the neurodegenerative process. Peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists, mainly thiazolidinediones, pioglitazone and rosiglitazone, have been successfully tested for their neuroprotective potential in PD experimental models, although the cellular target and underlying mechanism are currently a matter of debate. While the anti-inflammatory activity and attenuation of microgliosis have been proposed as a main mechanism of neuroprotection, other cellular targets might be involved, such as mitochondrial proteins controlling cellular bioenergetic and oxidative stress. Here, the current evidence of neuroprotection by PPAR-γ agonists in in vitro and in vivo experimental PD models is reported. Moreover, cellular pathways which have been investigated as potential targets of neuroprotection are reviewed. Taken together, the available data suggest that simultaneous targeting of multiple dysfunctional pathways may underlie the potent neuroprotective activity displayed by PPAR-γ agonists.

20 Review Modulating microglia activity with PPAR-γ agonists: a promising therapy for Parkinson's disease? 2013

Carta, Anna R / Pisanu, Augusta. ·Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy. acarta@unica.it ·Neurotox Res · Pubmed #22869006.

ABSTRACT: A dysregulated response of the neuroimmune system is a main contributor to the progression of neurodegeneration in Parkinson's disease (PD). Recent findings suggest that protracted activating stimuli including α-synuclein, drive microglia to acquire maladaptive functions and to assume a harmful phenotype that prevail over a restorative one. Based on this concept, disease-modifying drugs should be aimed at targeting suppression of harmful-activated microglia and the associated production of neurotoxic molecules as pro-inflammatory cytokines, while sparing or inducing beneficial-activated microglia. In this study, we review current evidence in support of the beneficial effect of targeting peroxisome-proliferator-activated receptor (PPAR)-γ to achieve neuroprotection in PD. PPAR-γ agonists as rosiglitazone and pioglitazone are currently gaining increasing attention as promising disease-modifying drugs in this disorder. Early in vitro studies, followed by studies in in vivo models of PD, have provided convincing evidence that these drugs inhibit neuronal degeneration likely by selectively targeting the expression of neurotoxic factors in reactive microglia. Potential therapeutic application has been corroborated by recent report of pioglitazone neuroprotective activity in a non-human primate model of PD. All together, preclinical evidence have prompted the translation of pioglitazone to a phase II clinical trial in early PD.

21 Review Contribution of pre-synaptic mechanisms to L-DOPA-induced dyskinesia. 2011

Carta, M / Bezard, E. ·Neurobiology Unit, Department of Experimental Medical Science, Lund University, BMC A11, Solvegatan 17, 22184 Lund, Sweden. manolocarta@unica.it ·Neuroscience · Pubmed #21840375.

ABSTRACT: Positron emission tomography (PET) imaging studies have shown that peak-dose dyskinesia is associated to abnormally high levels of synaptic dopamine (DA) in the caudate-putamen of dyskinetic L-DOPA-treated patients. High striatal extracellular DA levels have also been found in dyskinetic 6-OHDA-lesioned rats as compared to non-dyskinetic ones, suggesting that extracellular DA levels may play a key role in the induction of dyskinesia. In this article we review the evidences pointing to the serotonin system as the primary cause for the abnormally high levels of L-DOPA-derived extracellular DA in Parkinson's disease, and we discuss the feasibility of a therapeutic approach targeting this system.

22 Review Pharmacological therapy of Parkinson's disease: current options and new avenues. 2010

Simola, Nicola / Pinna, Annalisa / Fenu, Sandro. ·Department of Toxicology, University of Cagliari, Cagliari, Italy. nicola.simola@gmail.com ·Recent Pat CNS Drug Discov · Pubmed #20726838.

ABSTRACT: Parkinson's disease is a neurodegenerative pathology which affects the dopaminergic neurons in the mesencephalon, leading to a progressive and relentless motor disability and to non-motor symptoms of different severity. The aim of this review is to summarize the features of drugs currently used in the pharmacotherapy of Parkinson's disease, with a look at their beneficial effects and limitations. Drugs acting on dopamine transmission, as L-DOPA, direct dopaminergic agonists, inhibitors for either the MAO or COMT enzymes and drugs acting on neurotransmitters other than dopamine (e.g. acetylcholine, glutamate) will be covered. Investigational drugs currently under examination for their therapeutic potential in Parkinson's disease and recent patents which may be relevant to the field will be also discussed.

23 Review Pathophysiological roles for purines: adenosine, caffeine and urate. 2010

Morelli, Micaela / Carta, Anna R / Kachroo, Anil / Schwarzschild, Michael A. ·Department of Toxicology, University of Cagliari, Cagliari, Italy. morelli@unica.it ·Prog Brain Res · Pubmed #20696321.

ABSTRACT: The motor symptoms of Parkinson's disease (PD) are primarily due to the degeneration of the dopaminergic neurons in the nigrostriatal pathway. However, several other brain areas and neurotransmitters other than dopamine such as noradrenaline, 5-hydroxytryptamine and acetylcholine are affected in the disease. Moreover, adenosine because of the extensive interaction of its receptors with the dopaminergic system has been implicated in the pathophysiology of the disease. Based on the involvement of these non-dopaminergic neurotransmitters in PD and the sometimes severe adverse effects that limit the mainstay use of dopamine-based anti-parkinsonian treatments, recent assessments have called for a broadening of therapeutic options beyond the traditional dopaminergic drug arsenal. In this review we describe the interactions between dopamine and adenosine receptors that underpin the pre-clinical and clinical rationale for pursuing adenosine A(2A) receptor antagonists as symptomatic and potentially neuroprotective treatment of PD. The review will pay particular attention to recent results regarding specific A(2A) receptor-receptor interactions and recent findings identifying urate, the end product of purine metabolism, as a novel prognostic biomarker and candidate neuroprotectant in PD.

24 Clinical Trial Risk and predictors of dementia and parkinsonism in idiopathic REM sleep behaviour disorder: a multicentre study. 2019

Postuma, Ronald B / Iranzo, Alex / Hu, Michele / Högl, Birgit / Boeve, Bradley F / Manni, Raffaele / Oertel, Wolfgang H / Arnulf, Isabelle / Ferini-Strambi, Luigi / Puligheddu, Monica / Antelmi, Elena / Cochen De Cock, Valerie / Arnaldi, Dario / Mollenhauer, Brit / Videnovic, Aleksandar / Sonka, Karel / Jung, Ki-Young / Kunz, Dieter / Dauvilliers, Yves / Provini, Federica / Lewis, Simon J / Buskova, Jitka / Pavlova, Milena / Heidbreder, Anna / Montplaisir, Jacques Y / Santamaria, Joan / Barber, Thomas R / Stefani, Ambra / St Louis, Erik K / Terzaghi, Michele / Janzen, Annette / Leu-Semenescu, Smandra / Plazzi, Guiseppe / Nobili, Flavio / Sixel-Doering, Friederike / Dusek, Petr / Bes, Frederik / Cortelli, Pietro / Ehgoetz Martens, Kaylena / Gagnon, Jean-Francois / Gaig, Carles / Zucconi, Marco / Trenkwalder, Claudia / Gan-Or, Ziv / Lo, Christine / Rolinski, Michal / Mahlknecht, Philip / Holzknecht, Evi / Boeve, Angel R / Teigen, Luke N / Toscano, Gianpaolo / Mayer, Geert / Morbelli, Silvia / Dawson, Benjamin / Pelletier, Amelie. ·Department of Neurology, McGill University, Montreal General Hospital, Montreal, Canada. · Centre d'Études Avancées en Médecine du Sommeil, Hôpital du Sacré-Cœur de Montréal, Montréal, Canada. · Neurology Service, Hospital Clinic de Barcelona, IDIBAPS, CIBERNED, Barcelona, Spain. · Oxford Parkinson's Disease Centre (OPDC) and Oxford University, Oxford, UK. · Department of Neurology, Innsbruck Medical University, Innsbruck, Austria. · Mayo Clinic, Rochester, MN, USA. · Unit of Sleep Medicine and Epilepsy, IRCCS, C.Mondino Foundation, Pavia, Italy. · Department of Neurology, Philipps-Universität, Marburg, Germany. · Sleep disorders unit, Pitie-Salpetriere Hospital, IHU@ICM and Sorbonne University, Paris, France. · Sleep Disorders Center, Department of Neurology, Scientific Institute Ospedale San Raffaele, Vita-Salute University, Milan, Italy. · Sleep Center, Department of Cardiovascular and Neurological Sciences, University of Cagliari, Italy. · Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy. · IRCCS Institute of the Neurological Sciences, Ospedale Bellaria, ASL di Bologna, Bologna, Italy. · Sleep and Neurology Unit, Beau Soleil Clinic, Montpellier, France; EuroMov, University of Montpellier, Montpellier, France. · Clinical Neurology, Dept. of Neuroscience (DINOGMI), University of Genoa, and Polyclinic San Martino Hospital, Genoa, Italy. · Department of Neurosurgery (C.T.) University Medical Center, Göttingen; Paracelsus-Elena-Klinik (B.M., C.T. F. S-D.), Kassel, Germany. · Movement Disorders Unit and Division of Sleep Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, USA. · Department of Neurology and Centre of Clinical Neurosciences of the First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic. · Neuroscience Research Institute, Seoul National University College of Medicine, Department of Neurology, Seoul National University Hospital, Seoul, Korea. · Institute of Physiology Charité-Universitätsmedizin Berlin. Germany. · Sleep Unit, Department of Neurology, Hôpital Gui de Chauliac, Montpellier, INSERM U1061, Montpellier, F-34093 Cedex 5 France. · Department of Biomedical and Neuromotor Sciences, Bellaria Hospital, University of Bologna, Bologna, Italy. · IRCCS Institute of Neurological Sciences of Bologna, Bellaria Hospital, Bologna, Italy. · Brain and Mind Centre University of Sydney, Camperdown, Australia. · National Institute of Mental Health, Klecany, Third Faculty of Medicine, Charles Unviersity, Prague, Czech Republic. · Department of Neurology, Brigham and Women's Hospital, Boston; Harvard Medical School, Boston, USA. · Institute for Sleep Medicine and Neuromuscular Disorders, University Hospital Muenster, Muenster, Germany. · Department of Psychology, Université du Québec à Montréal, Montreal, Quebec, Canada. · Department of Human Genetics, McGill University, Montreal, Canada. · Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Canada. · Department of Neurology, Hephata Klinik, Schwalmstadt-Treysa, Germany. · Nuclear Medicine, Department of Health Sciences (DISSAL), University of Genoa and Polyclinic San Martino Hospital, Genoa, Italy. ·Brain · Pubmed #30789229.

ABSTRACT: Idiopathic REM sleep behaviour disorder (iRBD) is a powerful early sign of Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. This provides an unprecedented opportunity to directly observe prodromal neurodegenerative states, and potentially intervene with neuroprotective therapy. For future neuroprotective trials, it is essential to accurately estimate phenoconversion rate and identify potential predictors of phenoconversion. This study assessed the neurodegenerative disease risk and predictors of neurodegeneration in a large multicentre cohort of iRBD. We combined prospective follow-up data from 24 centres of the International RBD Study Group. At baseline, patients with polysomnographically-confirmed iRBD without parkinsonism or dementia underwent sleep, motor, cognitive, autonomic and special sensory testing. Patients were then prospectively followed, during which risk of dementia and parkinsonsim were assessed. The risk of dementia and parkinsonism was estimated with Kaplan-Meier analysis. Predictors of phenoconversion were assessed with Cox proportional hazards analysis, adjusting for age, sex, and centre. Sample size estimates for disease-modifying trials were calculated using a time-to-event analysis. Overall, 1280 patients were recruited. The average age was 66.3 ± 8.4 and 82.5% were male. Average follow-up was 4.6 years (range = 1-19 years). The overall conversion rate from iRBD to an overt neurodegenerative syndrome was 6.3% per year, with 73.5% converting after 12-year follow-up. The rate of phenoconversion was significantly increased with abnormal quantitative motor testing [hazard ratio (HR) = 3.16], objective motor examination (HR = 3.03), olfactory deficit (HR = 2.62), mild cognitive impairment (HR = 1.91-2.37), erectile dysfunction (HR = 2.13), motor symptoms (HR = 2.11), an abnormal DAT scan (HR = 1.98), colour vision abnormalities (HR = 1.69), constipation (HR = 1.67), REM atonia loss (HR = 1.54), and age (HR = 1.54). There was no significant predictive value of sex, daytime somnolence, insomnia, restless legs syndrome, sleep apnoea, urinary dysfunction, orthostatic symptoms, depression, anxiety, or hyperechogenicity on substantia nigra ultrasound. Among predictive markers, only cognitive variables were different at baseline between those converting to primary dementia versus parkinsonism. Sample size estimates for definitive neuroprotective trials ranged from 142 to 366 patients per arm. This large multicentre study documents the high phenoconversion rate from iRBD to an overt neurodegenerative syndrome. Our findings provide estimates of the relative predictive value of prodromal markers, which can be used to stratify patients for neuroprotective trials.

25 Clinical Trial Generalizing remotely supervised transcranial direct current stimulation (tDCS): feasibility and benefit in Parkinson's disease. 2018

Dobbs, Bryan / Pawlak, Natalie / Biagioni, Milton / Agarwal, Shashank / Shaw, Michael / Pilloni, Giuseppina / Bikson, Marom / Datta, Abhishek / Charvet, Leigh. ·New York University Langone Health, New York, USA. · Tufts School of Medicine, Boston, USA. · Department of Mechanical Chemical and Materials Engineering, University of Cagliari, Via Marengo 2, Cagliari, 09123, Italy. · City College of New York, New York, USA. · Soterix Medical, New York, USA. · New York University Langone Health, New York, USA. Leigh.charvet@nyumc.org. · NYU Comprehensive MS Care Center, 240 East 38th Street, 20th Floor, New York, NY, 10016, USA. Leigh.charvet@nyumc.org. ·J Neuroeng Rehabil · Pubmed #30522497.

ABSTRACT: BACKGROUND: Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that has been shown to improve common symptoms of neurological disorders like depressed mood, fatigue, motor deficits and cognitive dysfunction. tDCS requires daily treatment sessions in order to be effective. We developed a remotely supervised tDCS (RS-tDCS) protocol for participants with multiple sclerosis (MS) to increase accessibility of tDCS, reducing clinician, patient, and caregiver burden. The goal of this protocol is to facilitate home use for larger trials with extended treatment periods. In this study we determine the generalizability of RS-tDCS paired with cognitive training (CT) by testing its feasibility in participants with Parkinson's disease (PD). METHODS: Following the methods in our MS protocol development, we enrolled sixteen participants (n = 12 male, n = 4 female; mean age 66 years) with PD to complete ten open-label sessions of RS-tDCS paired with CT (2.0 mA × 20 min) at home under the remote supervision of a trained study technician. Tolerability data were collected before, during, and after each individual session. Baseline and follow-up measures included symptom inventories (fatigue and sleep) and cognitive assessments. RESULTS: RS-tDCS was feasible and tolerable for patients with PD, with at-home access leading to high protocol compliance. Side effects were mostly limited to mild sensations of transient itching and burning under the electrode sites. Similar to prior finding sin MS, we found preliminary efficacy for improvement of fatigue and cognitive processing speed in PD. CONCLUSIONS: RS-tDCS paired with CT is feasible for participants with PD to receive at home treatment. Signals of benefit for reduced fatigue and improved cognitive processing speed are consistent across the PD and MS samples. RS-tDCS can be generalized to provide tDCS to a range of patients with neurologic disorders for at-home rehabilitation. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02746705 . Registered April 21st 2016.

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