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Parkinson Disease: HELP
Articles from Milan area
Based on 723 articles published since 2010
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These are the 723 published articles about Parkinson Disease that originated from Milan area during 2010-2020.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5 · 6 · 7 · 8 · 9 · 10 · 11 · 12 · 13 · 14 · 15 · 16 · 17 · 18 · 19 · 20
1 Guideline ESPEN guideline clinical nutrition in neurology. 2018

Burgos, Rosa / Bretón, Irene / Cereda, Emanuele / Desport, Jean Claude / Dziewas, Rainer / Genton, Laurence / Gomes, Filomena / Jésus, Pierre / Leischker, Andreas / Muscaritoli, Maurizio / Poulia, Kalliopi-Anna / Preiser, Jean Charles / Van der Marck, Marjolein / Wirth, Rainer / Singer, Pierre / Bischoff, Stephan C. ·Nutritional Support Unit, University Hospital Vall d'Hebron, Barcelona, Spain. Electronic address: rburgos@vhebron.net. · Nutrition Unit, University Hospital Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain. · Nutrition and Dietetics Service, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; Fondazione Grigioni per il Morbo di Parkinson, Milano, Italy. · Nutrition Unit, ALS Centre, University Hospital of Limoges, Limoges, France. · Department of Neurology, University Hospital Münster, Germany. · Clinical Nutrition, Geneva University Hospitals, Geneva, Switzerland. · Cereneo (Center for Neurology and Rehabilitation) and University Department of Internal Medicine, Kantonsspital Aarau, Switzerland. · Department of Geriatrics, Alexianer Hospital Krefeld, Krefeld, Germany. · Department of Clinical Medicine, Sapienza, University of Rome, Rome, Italy. · Department of Nutrition, Laikon General Hospital, Athens, Greece. · Department of Intensive Care, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium. · Department of Geriatric Medicine, Radboud University Medical Center, Nijmegen, The Netherlands. · Department of Geriatric Medicine, Marien Hospital Herne, Ruhr-University Bochum, Germany. · Department of General Intensive Care and Institute for Nutrition Research, Rabin Medical Center, Beilinson Hospital, Tel Aviv University, Petah Tikva, Israel. · Institute of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany. ·Clin Nutr · Pubmed #29274834.

ABSTRACT: Neurological diseases are frequently associated with swallowing disorders and malnutrition. Moreover, patients with neurological diseases are at increased risk of micronutrient deficiency and dehydration. On the other hand, nutritional factors may be involved in the pathogenesis of neurological diseases. Multiple causes for the development of malnutrition in patients with neurological diseases are known including oropharyngeal dysphagia, impaired consciousness, perception deficits, cognitive dysfunction, and increased needs. The present evidence- and consensus-based guideline addresses clinical questions on best medical nutrition therapy in patients with neurological diseases. Among them, management of oropharyngeal dysphagia plays a pivotal role. The guideline has been written by a multidisciplinary team and offers 88 recommendations for use in clinical practice for amyotrophic lateral sclerosis, Parkinson's disease, stroke and multiple sclerosis.

2 Editorial The need for an extensive neuropsychological assessment for a reliable diagnosis of mild cognitive impairment in patients with Parkinson's disease. 2018

Daniele, A / Lacidogna, G. ·Institute of Neurology, Catholic University of Sacred Heart, Rome, Italy. ·Eur J Neurol · Pubmed #29509993.

ABSTRACT: -- No abstract --

3 Editorial Can a cognitive rehabilitation program in early stages of Parkinson's disease improve cognition, apathy and brain functional connectivity for up to 18 months? 2018

Daniele, A / Panza, F. ·Institute of Neurology, Catholic University of Sacred Heart, Rome, Italy. · Geriatric Unit and Gerontology-Geriatrics Research Laboratory, Department of Medical Sciences, IRCCS 'Casa Sollievo della Sofferenza', San Giovanni Rotondo, Italy. · Neurodegenerative Disease Unit, Department of Basic Medicine, Neuroscience and Sense Organs, University of Bari 'Aldo Moro', Bari, Italy. · Neurodegenerative Disease Unit, Department of Clinical Research in Neurology, University of Bari 'Aldo Moro', Azienda Ospedaliera 'Card. G. Panico', Tricase, Italy. ·Eur J Neurol · Pubmed #29215769.

ABSTRACT: -- No abstract --

4 Editorial Classifying tremor: Language matters. 2018

Albanese, Alberto. ·Department of Neurology, Humanitas Research Hospital, Rozzano, Milano, Italy. · Department of Neurology, Catholic University, Milano, Italy. ·Mov Disord · Pubmed #29193400.

ABSTRACT: -- No abstract --

5 Editorial GTP cyclohydrolase 1 mutations and Parkinson's disease: new insights beyond DOPA-responsive dystonia. 2015

Carecchio, Miryam / Schneider, Susanne A. ·Molecular Neurogentics Unit, C. Besta Institute, Milan, Italy. · Neurology Department, University of Kiel, Kiel, Germany. ·Mov Disord · Pubmed #26012785.

ABSTRACT: -- No abstract --

6 Editorial Novel perspectives for Parkinson's disease therapy: insights from the latest advances in disease pathophysiology, diagnostic and experimental tools and molecular targets. 2013

Spano, Pier Franco / Bellucci, Arianna. ·Department of Molecular and Translational Medicine National Institute of Neuroscience University of Brescia Brescia Italy. bellucci@med.unibs.it. ·CNS Neurol Disord Drug Targets · Pubmed #24040812.

ABSTRACT: -- No abstract --

7 Review Sex differences in steroid levels and steroidogenesis in the nervous system: Physiopathological role. 2019

Giatti, Silvia / Diviccaro, Silvia / Serafini, Melania Maria / Caruso, Donatella / Garcia-Segura, Luis Miguel / Viviani, Barbara / Melcangi, Roberto C. ·Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milano, Italy. · Instituto Cajal, Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain; Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, Madrid, Spain. · Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milano, Italy. Electronic address: roberto.melcangi@unimi.it. ·Front Neuroendocrinol · Pubmed #31689419.

ABSTRACT: The nervous system, in addition to be a target for steroid hormones, is the source of a variety of neuroactive steroids, which are synthesized and metabolized by neurons and glial cells. Recent evidence indicates that the expression of neurosteroidogenic proteins and enzymes and the levels of neuroactive steroids are different in the nervous system of males and females. We here summarized the state of the art of neuroactive steroids, particularly taking in consideration sex differences occurring in the synthesis and levels of these molecules. In addition, we discuss the consequences of sex differences in neurosteroidogenesis for the function of the nervous system under healthy and pathological conditions and the implications of neuroactive steroids and neurosteroidogenesis for the development of sex-specific therapeutic interventions.

8 Review Cognitive and psychiatric symptoms in genetically determined Parkinson's disease: a systematic review. 2019

Piredda, R / Desmarais, P / Masellis, M / Gasca-Salas, C. ·CINAC-HM Puerta del Sur, CEU-San Pablo University, Móstoles, Madrid, Spain. · Department of Neurology IRCCS, Istituto Clinico Humanitas Rozzano, Milano, Italy. · Cognitive and Movement Disorders Clinic, Sunnybrook Health Sciences Centre, Toronto, Canada. · L.C. Campbell Cognitive Neurology Research Unit, Sunnybrook Health Sciences Centre, Toronto, Canada. · Hurvitz Brain Sciences Program, Sunnybrook Research Institute, University of Toronto, Toronto, Canada. · Division of Neurology, Department of Medicine, University of Toronto, Toronto, Canada. · Institute of Medical Science, University of Toronto, Toronto, Canada. · CIBERNED, Institute Carlos III, Madrid, Spain. ·Eur J Neurol · Pubmed #31686421.

ABSTRACT: The aim was to review the existing reports on cognitive and behavioural symptoms in monogenic forms of Parkinson's disease (PD) and to identify recurring patterns of clinical manifestations in those with specific mutations. A systematic literature search was conducted to retrieve observational studies of monogenic PD. Data pertaining to cognitive and psychiatric manifestations were extracted using standardized templates. The PRISMA guidelines were followed. Of the 1889 citations retrieved, 95 studies on PD-related gene mutations were included: 35 in SNCA, 35 in LRRK2, four in VPS35, 10 in Parkin, three in DJ1 and eight in PINK1. Nineteen studies (20%) provided adequate data from comprehensive cognitive assessment and 31 studies (32.6%) outlined psychiatric manifestations through the use of neuropsychiatric scales. Cognitive impairment was reported in all monogenic PD forms with variable rates (58.8% PINK1, 53.9% SNCA, 50% DJ1, 29.2% VPS35, 15.7% LRRK2 and 7.4% Parkin). In this regard, executive functions and attention were the domains most affected. With respect to psychiatric symptoms, depression was the most frequent symptom, occurring in 37.5% of PINK1 cases and 41.7% of VPS35 and LRRK2 cases. Co-occurrence of cognitive decline with visual hallucinations was evidenced. Widespread accumulation of Lewy bodies, distinctive of SNCA, PINK1 and DJ1 mutations, results in higher rates of cognitive impairment. Similarly, a higher degree of visual hallucinations is observed in SNCA mutations, probably owing to the more widespread accumulation. The lower rates of α-synuclein pathology in LRRK2 and Parkin may underpin the more benign disease course in these patients.

9 Review The Link between Gaucher Disease and Parkinson's Disease Sheds Light on Old and Novel Disorders of Sphingolipid Metabolism. 2019

Indellicato, Rossella / Trinchera, Marco. ·Department of Health Science, University of Milan, 20142 Milano, Italy. · Department of Medicine and Surgery, University of Insubria, 21100 Varese, Italy. marco.trinchera@uninsubria.it. ·Int J Mol Sci · Pubmed #31284408.

ABSTRACT: Sphingolipid metabolism starts with the biosynthesis of ceramide, a bioactive lipid and the backbone for the biosynthesis of complex sphingolipids such as sphingomyelin and glycosphingolipids. These are degraded back to ceramide and then to sphingosine, which enters the ceramide-sphingosine-1-phosphate signaling pathway or is further degraded. Several enzymes with multiple catalytic properties and subcellular localizations are thus involved in such metabolism. Hereditary defects of lysosomal hydrolases have been known for several years to be the cause of lysosomal storage diseases such as gangliosidoses, Gaucher disease, Niemann-Pick disease, Krabbe disease, Fabry disease, and Farber disease. More recently, many other inborn errors of sphingolipid metabolism have been recognized, involving enzymes responsible for the biosynthesis of ceramide, sphingomyelin, and glycosphingolipids. Concurrently, epidemiologic and biochemical evidence has established a link between Gaucher disease and Parkinson's disease, showing that glucocerebrosidase variants predispose individuals to α-synuclein accumulation and neurodegeneration even in the heterozygous status. This appears to be due not only to lysosomal overload of non-degraded glucosylceramide, but to the derangement of vesicle traffic and autophagy, including mitochondrial autophagy, triggered by both sphingolipid intermediates and misfolded proteins. In this review, old and novel disorders of sphingolipid metabolism, in particular those of ganglioside biosynthesis, are evaluated in light of recent investigations of the link between Gaucher disease and Parkinson's disease, with the aim of better understanding their pathogenic mechanisms and addressing new potential therapeutic strategies.

10 Review Resting State Dynamic Functional Connectivity in Neurodegenerative Conditions: A Review of Magnetic Resonance Imaging Findings. 2019

Filippi, Massimo / Spinelli, Edoardo G / Cividini, Camilla / Agosta, Federica. ·Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy. · Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy. · Vita-Salute San Raffaele University, Milan, Italy. ·Front Neurosci · Pubmed #31281241.

ABSTRACT: In the last few decades, brain functional connectivity (FC) has been extensively assessed using resting-state functional magnetic resonance imaging (RS-fMRI), which is able to identify temporally correlated brain regions known as RS functional networks. Fundamental insights into the pathophysiology of several neurodegenerative conditions have been provided by studies in this field. However, most of these studies are based on the assumption of temporal stationarity of RS functional networks, despite recent evidence suggests that the spatial patterns of RS networks may change periodically over the time of an fMRI scan acquisition. For this reason, dynamic functional connectivity (dFC) analysis has been recently implemented and proposed in order to consider the temporal fluctuations of FC. These approaches hold promise to provide fundamental information for the identification of pathophysiological and diagnostic markers in the vast field of neurodegenerative diseases. This review summarizes the main currently available approaches for dFC analysis and reports their recent applications for the assessment of the most common neurodegenerative conditions, including Alzheimer's disease, Parkinson's disease, dementia with Lewy bodies, and frontotemporal dementia. Critical state-of-the-art findings, limitations, and future perspectives regarding the analysis of dFC in these diseases are provided from both a clinical and a technical point of view.

11 Review Neuronal microtubules and proteins linked to Parkinson's disease: a relevant interaction? 2019

Calogero, Alessandra M / Mazzetti, Samanta / Pezzoli, Gianni / Cappelletti, Graziella. ·Department of Biosciences, Università degli Studi di Milano, via Celoria 26, I-20133 Milan, Italy. · Fondazione Grigioni per il Morbo di Parkinson, via Zuretti 35, I-20135 Milan, Italy. · Parkinson Institute, ASST "G.Pini-CTO", via Bignami 1, I-20133 Milan, Italy. · Center of Excellence on Neurodegenerative Diseases, Università degli Studi di Milano, via Balzaretti, I-20133 Milan, Italy. ·Biol Chem · Pubmed #31256059.

ABSTRACT: Neuronal microtubules are key determinants of cell morphology, differentiation, migration and polarity, and contribute to intracellular trafficking along axons and dendrites. Microtubules are strictly regulated and alterations in their dynamics can lead to catastrophic effects in the neuron. Indeed, the importance of the microtubule cytoskeleton in many human diseases is emerging. Remarkably, a growing body of evidence indicates that microtubule defects could be linked to Parkinson's disease pathogenesis. Only a few of the causes of the progressive neuronal loss underlying this disorder have been identified. They include gene mutations and toxin exposure, but the trigger leading to neurodegeneration is still unknown. In this scenario, the evidence showing that mutated proteins in Parkinson's disease are involved in the regulation of the microtubule cytoskeleton is intriguing. Here, we focus on α-Synuclein, Parkin and Leucine-rich repeat kinase 2 (LRRK2), the three main proteins linked to the familial forms of the disease. The aim is to dissect their interaction with tubulin and microtubules in both physiological and pathological conditions, in which these proteins are overexpressed, mutated or absent. We highlight the relevance of such an interaction and suggest that these proteins could trigger neurodegeneration via defective regulation of the microtubule cytoskeleton.

12 Review Orthostatic hypotension and REM sleep behaviour disorder: impact on clinical outcomes in α-synucleinopathies. 2019

Pilotto, Andrea / Romagnolo, Alberto / Tuazon, Jasmine A / Vizcarra, Joaquin A / Marsili, Luca / Zibetti, Maurizio / Rosso, Michela / Rodriguez-Porcel, Federico / Borroni, Barbara / Rizzetti, Maria Cristina / Rossi, Carlo / Vizcarra-Escobar, Darwin / Molano, Jennifer R / Lopiano, Leonardo / Ceravolo, Roberto / Masellis, Mario / Espay, Alberto J / Padovani, Alessandro / Merola, Aristide. ·Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy. · Parkinson's Disease Rehabilitation Centre, FERB ONLUS - S. Isidoro Hospital, Trescore Balneario(BG), Italy. · Department of Neuroscience "Rita Levi Montalcini", University of Turin, Turin, Italy. · Gardner Family Center for Parkinson's Disease and Movement Disorders, Department of Neurology, University of Cincinnati, Cincinnati, Ohio, USA. · The Ohio State University College of Medicine, Columbus, Ohio, USA. · Department of Neurology, The State University of New York (SUNY) Downstate Medical Center, Brooklyn, New York, USA. · Department of Neurology, Medical University of South Carolina, Charleston, South Carolina, USA. · Unit of Neurology, "F. Lotti" Hospital, Pontedera, Italy. · Hypnos, Institutodel Sueño; Clinica San Felipe; Faculty of Medicine, Universidad PeruanaCayetano Heredia, Lima, Peru. · Department of Neurology and Rehabilitation Medicine, The University of Cincinnati, Cincinnati, Ohio, USA. · Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy. · Department of Medicine (Neurology) Hurvitz Brain Sciences Program, University of Toronto, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada. · Gardner Family Center for Parkinson's Disease and Movement Disorders, Department of Neurology, University of Cincinnati, Cincinnati, Ohio, USA aristidemerola@hotmail.com. ·J Neurol Neurosurg Psychiatry · Pubmed #31142660.

ABSTRACT: OBJECTIVE: Review the effect of orthostatic hypotension (OH) and rapid-eye-movement sleep behavioural disorder (RBD) on survival, cognitive impairment and postural stability, and discuss pathogenic mechanisms involved in the association of these two common non-motor features with relevant clinical outcomes in α-synucleinopathies. METHODS: We searched PubMed (January 2007-February 2019) for human studies of OH and RBD evaluating cognitive impairment, postural instability, and survival in Parkinson's disease (PD), dementia with Lewy bodies (DLB), multiple system atrophy (MSA) and pure autonomic failure (PAF). Included studies were analysed for design, key results and limitations as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: OH and RBD showed a positive association with cognitive impairment in PD and DLB, conflicting association in PAF, and no association in MSA. OH was correlated with incident falls and postural instability in PD and DLB but not in MSA. The association between RBD and postural instability was inconclusive; positive in five studies, negative in seven. OH, but not RBD, correlated with reduced survival in PD, DLB and MSA. The combination of OH and RBD was associated with cognitive impairment and more rapid progression of postural instability. CONCLUSIONS: OH and RBD yielded individual and combined negative effects on disability in α-synucleinopathies, reflecting a 'malignant' phenotype of PD with early cognitive impairment and postural instability. Underlying mechanisms may include involvement of selected brainstem cholinergic and noradrenergic nuclei.

13 Review None 2019

Riboldi, Giulietta M / Di Fonzo, Alessio B. ·The Marlene and Paolo Fresco Institute for Parkinson's and Movement Disorders, NYU Langone Health, New York, NY 10017, USA. giulietta.riboldi@nyulangone.org. · Dino Ferrari Center, Neuroscience Section, Department of Pathophysiology and Transplantation, University of Milan, 20122 Milan, Italy. giulietta.riboldi@nyulangone.org. · Dino Ferrari Center, Neuroscience Section, Department of Pathophysiology and Transplantation, University of Milan, 20122 Milan, Italy. alessio.difonzo@policlinico.mi.it. · Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Neurology Unit, 20122 Milan, Italy. alessio.difonzo@policlinico.mi.it. ·Cells · Pubmed #31010158.

ABSTRACT: Parkinson's disease (PD) is the second most common degenerative disorder. Although the disease was described more than 200 years ago, its pathogenetic mechanisms have not yet been fully described. In recent years, the discovery of the association between mutations of the

14 Review Are All Dopamine Agonists Essentially the Same? 2019

Torti, Margherita / Bravi, Daniele / Vacca, Laura / Stocchi, Fabrizio. ·IRCCS San Raffaele Pisana, Center for Parkinson Disease, Rome, Italy. · San Raffaele Cassino, Rome, Italy. · Lundbeck, Research and Development Department, Copenhagen, Denmark. · Casa di Cura privata Policlinico (CCPP), Milan, Italy. · IRCCS San Raffaele Pisana, Center for Parkinson Disease, Rome, Italy. fabrizio.stocchi@sanraffaele.it. · San Raffaele University, Rome, Italy. fabrizio.stocchi@sanraffaele.it. ·Drugs · Pubmed #30968290.

ABSTRACT: Dopamine agonists (DAs) represent an excellent treatment option for patients with Parkinson's disease, in both the early and advanced stages of the disease, improving motor symptoms, lowering the incidence of motor complications, and addressing several non-motor symptoms. Indeed, each of these compounds have different pharmacokinetic and pharmacodynamic properties, resulting in a unique efficacy and safety profile. Comorbidities, prominent non-motor symptoms and individual subjects' clinical characteristics should guide the choice of a specific DA, allowing better management of the patient by optimizing the DA benefit/risk ratio. In this article we discuss brain distribution of dopamine receptors and their role in each of the dopaminergic pathways, the pharmacological profile of non-ergoline DAs and class-related adverse effects, as reported from post-marketing studies.

15 Review Resting-state Functional MRI in Parkinsonian Syndromes. 2019

Filippi, Massimo / Sarasso, Elisabetta / Agosta, Federica. ·Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute Vita-Salute San Raffaele University Milan Italy. · Department of Neurology, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute Vita-Salute San Raffaele University Milan Italy. · Laboratory of Movement Analysis San Raffaele Scientific Institute Milan Italy. ·Mov Disord Clin Pract · Pubmed #30838308.

ABSTRACT: Background: Functional MRI (fMRI) has been widely used to study abnormal patterns of functional connectivity at rest in patients with movement disorders such as idiopathic Parkinson's disease (PD) and atypical parkinsonisms. Methods: This manuscript provides an educational review of the current use of resting-state fMRI in the field of parkinsonian syndromes. Results: Resting-state fMRI studies have improved the current knowledge about the mechanisms underlying motor and non-motor symptom development and progression in movement disorders. Even if its inclusion in clinical practice is still far away, resting-state fMRI has the potential to be a promising biomarker for early disease detection and prediction. It may also aid in differential diagnosis and monitoring brain responses to therapeutic agents and neurorehabilitation strategies in different movement disorders. Conclusions: There is urgent need to identify and validate prodromal biomarkers in PD patients, to perform further studies assessing both overlapping and disease-specific fMRI abnormalities among parkinsonian syndromes, and to continue technical advances to fully realize the potential of fMRI as a tool to monitor the efficacy of chronic therapies.

16 Review Do Th17 Lymphocytes and IL-17 Contribute to Parkinson's Disease? A Systematic Review of Available Evidence. 2019

Storelli, Elisa / Cassina, Niccolò / Rasini, Emanuela / Marino, Franca / Cosentino, Marco. ·Center of Research in Medical Pharmacology, University of Insubria, Varese, Italy. ·Front Neurol · Pubmed #30733703.

ABSTRACT: Parkinson's disease (PD) is a neurodegenerative disease characterized by progressive loss of dopaminergic neurons, appearance of Lewy bodies and presence of neuroinflammation. No treatments currently exist to prevent PD or delay its progression, and dopaminergic substitution treatments just relieve the consequences of dopaminergic neuron loss. Increasing evidence points to peripheral T lymphocytes as key players in PD, and recently there has been growing interest into the specific role of T helper (Th) 17 lymphocytes. Th17 are a proinflammatory CD4+ T cell lineage named after interleukin (IL)-17, the main cytokine produced by these cells. Th17 are involved in immune-related disease such as psoriasis, rheumatoid arthritis and inflammatory bowel disease, and drugs targeting Th17/IL-17 are currently approved for clinical use in such disease. In the present paper, we first summarized current knowledge about contribution of the peripheral immune system in PD, as well as about the physiopharmacology of Th17 and IL-17 together with its therapeutic relevance. Thereafter, we systematically retrieved and evaluated published evidence about Th17 and IL-17 in PD, to help assessing Th17/IL-17-targeting drugs as potentially novel antiparkinson agents. Critical appraisal of the evidence did not allow to reach definite conclusions: both animal as well as clinical studies are limited, just a few provide mechanistic evidence and none of them investigates the eventual relationship between Th17/IL-17 and clinically relevant endpoints such as disease progression, disability scores, intensity of dopaminergic substitution treatment. Careful assessment of Th17 in PD is anyway a priority, as Th17/IL-17-targeting therapeutics might represent a straightforward opportunity for the unmet needs of PD patients.

17 Review α-Synuclein and Glia in Parkinson's Disease: A Beneficial or a Detrimental Duet for the Endo-Lysosomal System? 2019

Filippini, Alice / Gennarelli, Massimo / Russo, Isabella. ·Biology and Genetic Unit, Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123, Brescia, Italy. · Genetics Unit, IRCCS Istituto Centro S. Giovanni di Dio, Fatebenefratelli, 25123, Brescia, Italy. · Biology and Genetic Unit, Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123, Brescia, Italy. isabella.russo@unibs.it. ·Cell Mol Neurobiol · Pubmed #30637614.

ABSTRACT: Accumulation of α-synuclein (α-syn) species in dopaminergic neurons is one of the main hallmarks of Parkinson's disease (PD). Several factors have been associated with α-syn aggregation process, including an impairment of the proper protein degradation, which might drive the neurons toward an alternative and/or additional clearance mechanism that involves the release of undigested material from the cell. It has been reported that extracellular α-syn, released by stressed and/or degenerating neurons, might widely contribute to the neuronal toxicity and degeneration. Therefore, the uptake and clearance of misfolded/aggregated proteins is a key process to control extracellular deposition of α-syn aggregates, the spreading and progression of the disease. All the main brain cell types, neurons, astrocytes and microglia are able to internalize and degrade extracellular α-syn, however, glial cells appear to be the most efficient scavengers. Accumulating evidence indicates that the endocytosis of α-syn species might be conformation-sensitive, cell- and receptor-type specific, making the scenario highly complex. In this review, we will shed light on the different endocytosis mechanisms and receptors recruited for the uptake and clearance of pathological α-syn forms with a special focus on glial cells. Moreover, we will discuss how PD-related genes, in addition to α-syn itself, may alter the endo-lysosomal pathway causing an impairment of clearance, which, in turn, lead to accumulation of toxic species, dysfunctions of glia physiology and progression of the disease.

18 Review What is the Healthy Gut Microbiota Composition? A Changing Ecosystem across Age, Environment, Diet, and Diseases. 2019

Rinninella, Emanuele / Raoul, Pauline / Cintoni, Marco / Franceschi, Francesco / Miggiano, Giacinto Abele Donato / Gasbarrini, Antonio / Mele, Maria Cristina. ·UOC di Nutrizione Clinica, Dipartimento di Scienze Gastroenterologiche, Endocrino-Metaboliche e Nefro-Urologiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy. emanuele.rinninella@unicatt.it. · Istituto di Patologia Speciale Medica, Università Cattolica del Sacro Cuore, 00168 Rome, Italy. emanuele.rinninella@unicatt.it. · Istituto di Patologia Speciale Medica, Università Cattolica del Sacro Cuore, 00168 Rome, Italy. pauline.raoul1@gmail.com. · Scuola di Specializzazione in Scienza dell'Alimentazione, Università di Roma Tor Vergata, 00133 Rome, Italy. marco.cintoni@gmail.com. · UOC di Medicina d'Urgenza e Pronto Soccorso, Dipartimento di Scienze dell'Emergenza, Anestesiologiche e della Rianimazione, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy. francesco.franceschi@unicatt.it. · Istituto di Medicina Interna e Geriatria, Università Cattolica del Sacro Cuore, 00168 Rome, Italy. francesco.franceschi@unicatt.it. · UOC di Nutrizione Clinica, Dipartimento di Scienze Gastroenterologiche, Endocrino-Metaboliche e Nefro-Urologiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy. giacintoabele.miggiano@unicatt.it. · Istituto di Patologia Speciale Medica, Università Cattolica del Sacro Cuore, 00168 Rome, Italy. giacintoabele.miggiano@unicatt.it. · Istituto di Patologia Speciale Medica, Università Cattolica del Sacro Cuore, 00168 Rome, Italy. antonio.gasbarrini@unicatt.it. · UOC di Medicina Interna e Gastroenterologia, Dipartimento di Scienze Gastroenterologiche, Endocrino-Metaboliche e Nefro-Urologiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy. antonio.gasbarrini@unicatt.it. · UOC di Nutrizione Clinica, Dipartimento di Scienze Gastroenterologiche, Endocrino-Metaboliche e Nefro-Urologiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy. mariacristina.mele@unicatt.it. · Istituto di Patologia Speciale Medica, Università Cattolica del Sacro Cuore, 00168 Rome, Italy. mariacristina.mele@unicatt.it. ·Microorganisms · Pubmed #30634578.

ABSTRACT: Each individual is provided with a unique gut microbiota profile that plays many specific functions in host nutrient metabolism, maintenance of structural integrity of the gut mucosal barrier, immunomodulation, and protection against pathogens. Gut microbiota are composed of different bacteria species taxonomically classified by genus, family, order, and phyla. Each human's gut microbiota are shaped in early life as their composition depends on infant transitions (birth gestational date, type of delivery, methods of milk feeding, weaning period) and external factors such as antibiotic use. These personal and healthy core native microbiota remain relatively stable in adulthood but differ between individuals due to enterotypes, body mass index (BMI) level, exercise frequency, lifestyle, and cultural and dietary habits. Accordingly, there is not a unique optimal gut microbiota composition since it is different for each individual. However, a healthy host⁻microorganism balance must be respected in order to optimally perform metabolic and immune functions and prevent disease development. This review will provide an overview of the studies that focus on gut microbiota balances in the same individual and between individuals and highlight the close mutualistic relationship between gut microbiota variations and diseases. Indeed, dysbiosis of gut microbiota is associated not only with intestinal disorders but also with numerous extra-intestinal diseases such as metabolic and neurological disorders. Understanding the cause or consequence of these gut microbiota balances in health and disease and how to maintain or restore a healthy gut microbiota composition should be useful in developing promising therapeutic interventions.

19 Review Beta2-Adrenoceptor Agonists in Parkinson's Disease and Other Synucleinopathies. 2019

Magistrelli, Luca / Comi, Cristoforo. ·Movement Disorders Centre, Neurology Unit, Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy. · PhD Program in Clinical and Experimental Medicine and Medical Humanities, University of Insubria, Varese, Italy. · Movement Disorders Centre, Neurology Unit, Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy. cristoforo.comi@med.uniupo.it. · Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), University of Piemonte Orientale, Novara, Italy. cristoforo.comi@med.uniupo.it. ·J Neuroimmune Pharmacol · Pubmed #30617750.

ABSTRACT: Evidence supporting the use of β2AR agonists in synucleinopathies is rapidly growing. Findings come from different scientific approaches. Molecular and immunological data suggest that adrenergic stimulation may decrease both α-synuclein (α-syn) deposition and pro-inflammatory/neurotoxic molecules release. Small open label clinical trials including a total number of 25 Parkinson's disease (PD) patients, in which the β2AR agonist salbutamol was added to levodopa, suggest a promising symptomatic benefit. In line with these findings, epidemiological studies investigating the risk of PD development suggest that long term exposure to the agonist salbutamol might be protective, while the antagonist propranolol possibly detrimental. Nonetheless, in both lines of investigation the studies performed so far present important limitations. On the clinical side, large randomized controlled trials are lacking, whereas on the epidemiological side the presence of co-morbid conditions (i.e. smoking and essential tremor) potentially influencing PD risk should taken into consideration. In summary, it is our opinion that β2AR stimulation in synucleinopathies has a rationale and therefore merits further investigation. Graphical Abstract ᅟ.

20 Review Living in Promiscuity: The Multiple Partners of Alpha-Synuclein at the Synapse in Physiology and Pathology. 2019

Longhena, Francesca / Faustini, Gaia / Spillantini, Maria Grazia / Bellucci, Arianna. ·Division of Pharmacology, Department of molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123, Brescia, Italy. f.longhena@unibs.it. · Division of Pharmacology, Department of molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123, Brescia, Italy. g.faustini004@unibs.it. · Department of Clinical Neurosciences, Clifford Allbutt Building, University of Cambridge, Cambridge CB2 0AH, UK. mgs11@cam.ac.uk. · Division of Pharmacology, Department of molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123, Brescia, Italy. arianna.bellucci@unibs.it. · Laboratory for Preventive and Personalized Medicine, Department of molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123, Brescia, Italy. arianna.bellucci@unibs.it. ·Int J Mol Sci · Pubmed #30609739.

ABSTRACT: Alpha-synuclein (α-syn) is a small protein that, in neurons, localizes predominantly to presynaptic terminals. Due to elevated conformational plasticity, which can be affected by environmental factors, in addition to undergoing disorder-to-order transition upon interaction with different interactants, α-syn is counted among the intrinsically disordered proteins (IDPs) family. As with many other IDPs, α-syn is considered a hub protein. This function is particularly relevant at synaptic sites, where α-syn is abundant and interacts with many partners, such as monoamine transporters, cytoskeletal components, lipid membranes, chaperones and synaptic vesicles (SV)-associated proteins. These protein⁻protein and protein⁻lipid membrane interactions are crucial for synaptic functional homeostasis, and alterations in α-syn can cause disruption of this complex network, and thus a failure of the synaptic machinery. Alterations of the synaptic environment or post-translational modification of α-syn can induce its misfolding, resulting in the formation of oligomers or fibrillary aggregates. These α-syn species are thought to play a pathological role in neurodegenerative disorders with α-syn deposits such as Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), which are referred to as synucleinopathies. Here, we aim at revising the complex and promiscuous role of α-syn at synaptic terminals in order to decipher whether α-syn molecular interactants may influence its conformational state, contributing to its aggregation, or whether they are just affected by it.

21 Review Glucocerebrosidase mutations and synucleinopathies: Toward a model of precision medicine. 2019

Blandini, Fabio / Cilia, Roberto / Cerri, Silvia / Pezzoli, Gianni / Schapira, Anthony H V / Mullin, Stephen / Lanciego, José L. ·Laboratory of Functional Neurochemistry, IRCCS Mondino Foundation, Pavia, Italy. · Parkinson Institute, ASST Gaetano Pini-CTO, Milan, Italy. · Department of Clinical Neurosciences, Institute of Neurology, University College London, Hampstead, UK. · Institute of Translational and Stratified Medicine, Plymouth University Peninsula School of Medicine, Plymouth, UK. · Programa de Neurociencias, Fundación para la Investigación Médica Aplicada (FIMA), Universidad de Navarra, Pamplona, Spain. · Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CiberNed), Madrid, Spain. · Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain. ·Mov Disord · Pubmed #30589955.

ABSTRACT: Glucocerebrosidase is a lysosomal enzyme. The characterization of a direct link between mutations in the gene coding for glucocerebrosidase (GBA1) with the development of Parkinson's disease and dementia with Lewy bodies has heightened interest in this enzyme. Although the mechanisms through which glucocerebrosidase regulates the homeostasis of α-synuclein remains poorly understood, the identification of reduced glucocerebrosidase activity in the brains of patients with PD and dementia with Lewy bodies has paved the way for the development of novel therapeutic strategies directed at enhancing glucocerebrosidase activity and reducing α-synuclein burden, thereby slowing down or even preventing neuronal death. Here we reviewed the current literature relating to the mechanisms underlying the cross talk between glucocerebrosidase and α-synuclein, the GBA1 mutation-associated clinical phenotypes, and ongoing therapeutic approaches targeting glucocerebrosidase. © 2018 International Parkinson and Movement Disorder Society.

22 Review Dopamine, Oxidative Stress and Protein-Quinone Modifications in Parkinson's and Other Neurodegenerative Diseases. 2019

Monzani, Enrico / Nicolis, Stefania / Dell'Acqua, Simone / Capucciati, Andrea / Bacchella, Chiara / Zucca, Fabio A / Mosharov, Eugene V / Sulzer, David / Zecca, Luigi / Casella, Luigi. ·Department of Chemistry, University of Pavia, 27100, Pavia, Italy. · Institute of Biomedical Technologies, National Research Council of Italy, Segrate (Milano), Italy. · Department of Psychiatry, Columbia University Medical Center, New York State Psychiatric Institute, New York, NY, USA. · Departments of Neurology and Pharmacology, Columbia University Medical Center, New York, NY, USA. ·Angew Chem Int Ed Engl · Pubmed #30536578.

ABSTRACT: Dopamine (DA) is the most important catecholamine in the brain, as it is the most abundant and the precursor of other neurotransmitters. Degeneration of nigrostriatal neurons of substantia nigra pars compacta in Parkinson's disease represents the best-studied link between DA neurotransmission and neuropathology. Catecholamines are reactive molecules that are handled through complex control and transport systems. Under normal conditions, small amounts of cytosolic DA are converted to neuromelanin in a stepwise process involving melanization of peptides and proteins. However, excessive cytosolic or extraneuronal DA can give rise to nonselective protein modifications. These reactions involve DA oxidation to quinone species and depend on the presence of redox-active transition metal ions such as iron and copper. Other oxidized DA metabolites likely participate in post-translational protein modification. Thus, protein-quinone modification is a heterogeneous process involving multiple DA-derived residues that produce structural and conformational changes of proteins and can lead to aggregation and inactivation of the modified proteins.

23 Review Peripheral Immunity, Immunoaging and Neuroinflammation in Parkinson's Disease. 2019

Kustrimovic, Natasa / Marino, Franca / Cosentino, Marco. ·Center of Research in Medical Pharmacology, University of Insubria, Varese, Italy. ·Curr Med Chem · Pubmed #30306855.

ABSTRACT: Parkinson's disease (PD) is the second most common neurodegenerative disorder among elderly population, characterized by the progressive degeneration of dopaminergic neurons in the midbrain. To date, exact cause remains unknown and the mechanism of neurons death uncertain. It is typically considered as a disease of central nervous system (CNS). Nevertheless, numerous evidence has been accumulated in several past years testifying undoubtedly about the principal role of neuroinflammation in progression of PD. Neuroinflammation is mainly associated with presence of activated microglia in brain and elevated levels of cytokine levels in CNS. Nevertheless, active participation of immune system as well has been noted, such as, elevated levels of cytokine levels in blood, the presence of auto antibodies, and the infiltration of T cell in CNS. Moreover, infiltration and reactivation of those T cells could exacerbate neuroinflammation to greater neurotoxic levels. Hence, peripheral inflammation is able to prime microglia into pro-inflammatory phenotype, which can trigger stronger response in CNS further perpetuating the on-going neurodegenerative process. In the present review, the interplay between neuroinflammation and the peripheral immune response in the pathobiology of PD will be discussed. First of all, an overview of regulation of microglial activation and neuroinflammation is summarized and discussed. Afterwards, we try to collectively analyze changes that occurs in peripheral immune system of PD patients, suggesting that these peripheral immune challenges can exacerbate the process of neuroinflammation and hence the symptoms of the disease. In the end, we summarize some of proposed immunotherapies for treatment of PD.

24 Review Pharmacokinetic drug evaluation of CVT-301 for the treatment of Parkinson's disease. 2018

Stocchi, Fabrizio / Vacca, Laura / Stirpe, Paola / Torti, Margherita. ·a Departement of Neurology , University and Institute for Research and Medical Care, San Raffaele Rome , Roma , Italy. · b Department of Neurorehabilitation Sciences , Casa Cura Policlinico (CCP) , Milan , Italy. · c Departement of Neurology , Institute for Research and Medical Care, San Raffaele Cassino , Cassino (FR) , Italy. ·Expert Opin Drug Metab Toxicol · Pubmed #30479171.

ABSTRACT: INTRODUCTION: Levodopa (LD), in combination with a decarboxylase inhibitor, is a mainstay and the most effective therapeutic agent in the treatment of Parkinson's disease (PD). Unfortunately, during chronic treatment with this agent, ON-OFF phenomena and dyskinesia appear. Despite the many medical treatment options available, unpredictable OFF episodes can still occur and be severe and disabling. A rescue therapy that provides a rapid and predictable ON response for patients with OFF periods would be of great value for such patients. Areas covered: CVT-301 is a self-administered dry powder aerosol inhaled formulation of LD that is being developed as a self-administered treatment for OFF periods. The PK profile of CVT-301, the efficacy, and the safety highlighted in randomized clinical trials will be reviewed. Expert opinion: CVT-301 may offer several potential advantages including increased systemic bioavailability through pulmonary absorption, rapid onset of action, avoidance of first-pass drug metabolism and less plasma-level variability. List of Abbreviations: PD: Parkinson's disease; LD: Levodopa; CD: Carbidopa; AADC: aromatic L-amino acid decarboxylase; IR: immediate-release; FPD: fine particle dose; GI: gastrointestinal; PK: pharmacokinetic; CVs: coefficient of variation; UPDRS: Unified Parkinson's Disease Rating Scale; AEs: adverse events; FEV: forced expiratory volume; FVC: forced vital capacity; DL

25 Review Functional MRI in Idiopathic Parkinson's Disease. 2018

Filippi, Massimo / Elisabetta, Sarasso / Piramide, Noemi / Agosta, Federica. ·Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, Vita-Salute San Raffaele University, Milan, Italy; Department of Neurology, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy. Electronic address: filippi.massimo@hsr.it. · Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, Vita-Salute San Raffaele University, Milan, Italy; Laboratory of Movement Analysis, San Raffaele Scientific Institute, Milan, Italy. · Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, Vita-Salute San Raffaele University, Milan, Italy. ·Int Rev Neurobiol · Pubmed #30314606.

ABSTRACT: Functional MRI (fMRI) has been widely used to study abnormal patterns of brain connectivity at rest and activation during a variety of tasks in patients with idiopathic Parkinson's disease (PD). fMRI studies in PD have led to a better understanding of many aspects of the disease including both motor and non-motor symptoms. Although its translation into clinical practice is still at an early stage, fMRI measures hold promise for multiple clinical applications in PD, including the early detection, predicting future change in clinical status, and as a marker of alterations in brain physiology related to neurotherapeutic agents and neurorehabilitative strategies.

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