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Parkinson Disease: HELP
Articles by Vincenzo Silani
Based on 9 articles published since 2010
(Why 9 articles?)
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Between 2010 and 2020, V. Silani wrote the following 9 articles about Parkinson Disease.
 
+ Citations + Abstracts
1 Review The synaptic function of parkin. 2017

Sassone, Jenny / Serratto, GiuliaMaia / Valtorta, Flavia / Silani, Vincenzo / Passafaro, Maria / Ciammola, Andrea. ·San Raffaele Scientific Institute and Vita-Salute University, Milan, Italy. · CNR Institute of Neuroscience, Department BIOMETRA, Università degli Studi di Milano, Milan, Italy. · IRCCS Istituto Auxologico Italiano, Department of Neurology and Laboratory of Neuroscience, Milan, Italy. · Department of Pathophysiology and Transplantation, 'Dino Ferrari' Centre, Università degli Studi di Milano, Milan, Italy. ·Brain · Pubmed #28335015.

ABSTRACT: Loss of function mutations in the gene PARK2, which encodes the protein parkin, cause autosomal recessive juvenile parkinsonism, a neurodegenerative disease characterized by degeneration of the dopaminergic neurons localized in the substantia nigra pars compacta. No therapy is effective in slowing disease progression mostly because the pathogenesis of the disease is yet to be understood. From accruing evidence suggesting that the protein parkin directly regulates synapses it can be hypothesized that PARK2 gene mutations lead to early synaptic damage that results in dopaminergic neuron loss over time. We review evidence that supports the role of parkin in modulating excitatory and dopaminergic synapse functions. We also discuss how these findings underpin the concept that autosomal recessive juvenile parkinsonism can be primarily a synaptopathy. Investigation into the molecular interactions between parkin and synaptic proteins may yield novel targets for pharmacologic interventions.

2 Review Angiogenin variants in Parkinson disease and amyotrophic lateral sclerosis. 2011

van Es, Michael A / Schelhaas, Helenius J / van Vught, Paul W J / Ticozzi, Nicola / Andersen, Peter M / Groen, Ewout J N / Schulte, Claudia / Blauw, Hylke M / Koppers, Max / Diekstra, Frank P / Fumoto, Katsumi / LeClerc, Ashley Lyn / Keagle, Pamela / Bloem, Bastiaan R / Scheffer, Hans / van Nuenen, Bart F L / van Blitterswijk, Marka / van Rheenen, Wouter / Wills, Anne-Marie / Lowe, Patrick P / Hu, Guo-fu / Yu, Wenhao / Kishikawa, Hiroko / Wu, David / Folkerth, Rebecca D / Mariani, Claudio / Goldwurm, Stefano / Pezzoli, Gianni / Van Damme, Philip / Lemmens, Robin / Dahlberg, Caroline / Birve, Anna / Fernández-Santiago, Rubén / Waibel, Stefan / Klein, Christine / Weber, Markus / van der Kooi, Anneke J / de Visser, Marianne / Verbaan, Dagmar / van Hilten, Jacobus J / Heutink, Peter / Hennekam, Eric A M / Cuppen, Edwin / Berg, Daniela / Brown, Robert H / Silani, Vincenzo / Gasser, Thomas / Ludolph, Albert C / Robberecht, Wim / Ophoff, Roel A / Veldink, Jan H / Pasterkamp, R Jeroen / de Bakker, Paul I W / Landers, John E / van de Warrenburg, Bart P / van den Berg, Leonard H. ·Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, The Netherlands. ·Ann Neurol · Pubmed #22190368.

ABSTRACT: OBJECTIVE: Several studies have suggested an increased frequency of variants in the gene encoding angiogenin (ANG) in patients with amyotrophic lateral sclerosis (ALS). Interestingly, a few ALS patients carrying ANG variants also showed signs of Parkinson disease (PD). Furthermore, relatives of ALS patients have an increased risk to develop PD, and the prevalence of concomitant motor neuron disease in PD is higher than expected based on chance occurrence. We therefore investigated whether ANG variants could predispose to both ALS and PD. METHODS: We reviewed all previous studies on ANG in ALS and performed sequence experiments on additional samples, which allowed us to analyze data from 6,471 ALS patients and 7,668 controls from 15 centers (13 from Europe and 2 from the USA). We sequenced DNA samples from 3,146 PD patients from 6 centers (5 from Europe and 1 from the USA). Statistical analysis was performed using the variable threshold test, and the Mantel-Haenszel procedure was used to estimate odds ratios. RESULTS: Analysis of sequence data from 17,258 individuals demonstrated a significantly higher frequency of ANG variants in both ALS and PD patients compared to control subjects (p = 9.3 × 10(-6) for ALS and p = 4.3 × 10(-5) for PD). The odds ratio for any ANG variant in patients versus controls was 9.2 for ALS and 6.7 for PD. INTERPRETATION: The data from this multicenter study demonstrate that there is a strong association between PD, ALS, and ANG variants. ANG is a genetic link between ALS and PD.

3 Article A Novel Approach for Investigating Parkinson's Disease Personality and Its Association With Clinical and Psychological Aspects. 2019

Carelli, Laura / Solca, Federica / Torre, Silvia / Pasquini, Jacopo / Morelli, Claudia / Pezzati, Rita / Mancini, Francesca / Ciammola, Andrea / Silani, Vincenzo / Poletti, Barbara. ·Department of Neurology and Laboratory of Neuroscience, Italian Auxological Institute (IRCCS), Milan, Italy. · Department of Pathophysiology and Transplantation, "Dino Ferrari" Center, University of Milan, Milan, Italy. · Department of Business Economics, Health and Social Care, University of Applied Sciences and Arts of Southern Switzerland, Manno, Switzerland. · Centro Terapia Cognitiva, Como, Italy. ·Front Psychol · Pubmed #31681080.

ABSTRACT: Objective: A complex relationship between neuropsychiatric symptoms, personality traits and neurochemical changes in patients with Parkinson's disease (PD) has been highlighted in the past several decades. In particular, a specific Parkinson personality with obsessive traits has been described. However, despite the great amount of anecdotal evidence, this aspect, together with its neurobiological, psychological and clinical correlates, are still not clearly defined. Therefore, we performed a case-control study in order to investigate the presence and rate of obsessive personality traits in PD patients within the theoretical framework of cognitive-constructivist model. Moreover, the relationship between PD personality and clinical, psychological and quality of life (QoL) aspects in PD were investigated. Methods: Fifty-one non-demented patients with probable or possible PD (not demented) were recruited at the inpatient-outpatient San Luca Hospital, IRCCS Istituto Auxologico Italiano. Control group was composed by forty-eight age- and education-matched healthy volunteers. Patients underwent a neurological investigation including Unified PD Rating Scale (UPDRS), Modified Hoehn and Yahr and Schwab and England staging scales. The following psychological questionnaires were administered to the overall sample: Personal Meaning Questionnaire (PMQ), State-Trait Anxiety Inventory-Form Y (STAI-Y), Beck Depression Inventory (BDI), Symptom Check List-90 (SCL-90), Short-Form Health Survey-36 (SF-36). Results: No significant differences in personality styles were observed in PD patients and controls, with a prevalence of phobic personal meaning organization (PMO) in both groups. However, PD patients showed more anxiety, depression and obsessive-compulsive (OC) symptoms than controls at the psychological questionnaires, as well as poorer QoL levels. The intensity of personality traits, and in particular for the obsessive personality style, were negatively associated with QoL and positively with disease severity. No significant relationships were observed between personality and other clinical aspects, such as side of onset and disease duration. Conclusion: Parkinson's disease patients did not show a different personality profile according to the cognitive-constructivist model with respect to controls. However, in this population, a general enhancement in the tendency to codify experience by means of specific cognitive and emotional patterns was associated to disease progression and to a poorer QoL.

4 Article Real life evaluation of safinamide effectiveness in Parkinson's disease. 2018

Mancini, Francesca / Di Fonzo, Alessio / Lazzeri, Giulia / Borellini, Linda / Silani, Vincenzo / Lacerenza, Marco / Comi, Cristoforo. ·Department of Neurology-Stroke Unit and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan, Italy. Francesca.mancini@tin.it. · Neurology Unit, IRCCS Fondazione Ca' Granda Ospedale Maggiore Policlinico, "Dino Ferrari" Center, Neuroscience Section, Department of Pathophysiology and Transplantation, Università Degli Studi di Milano, Milan, Italy. · Neuropathophysiology Unit, IRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy. · Department of Neurology-Stroke Unit and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan, Italy. · Department of Neurology-Stroke Unit and Laboratory of Neuroscience, "Dino Ferrari" Centre - Centre for Neurotechnology and Brain Therapeutics, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy. · Neurology Service, Casa di Cura Humanitas San Pio X, Milan, Italy. · Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy. ·Neurol Sci · Pubmed #29441484.

ABSTRACT: In this retrospective study, we evaluated both efficacy and effectiveness of safinamide 50 and 100 mg in the treatment of motor fluctuations and disabling dyskinesias in a cohort of patients with idiopathic Parkinson's disease (PD). Ninety-one PD patients were evaluated during the first year of commercialization of the drug, both prior to starting safinamide and at the last available follow-up. Evaluations were based on the Unified Parkinson's Disease Scale part III (UPDRS III), Hoehn & Yahr (HY), Unified Dyskinesia Rating Scale (UDysRS) walking and balance item 9 score, daily time spent in OFF and in ON with disabling dyskinesias (1 week diary), mean daily dose of levodopa (LD), dopamine-agonists (DA), catechol-O-methyl transferase inhibitor (COMT-I), monoamine oxidase B inhibitor (MAOB-I), and their LD equivalent dose (LEDD). Eight patients withdrew safinamide within the first month for minor side effects. At the follow-up evaluation, after a mean time with safinamide of 7.5 months ± 3.4, all patients showed a significant improvement of all the scale scores, except for HY, and of the daily dosages of the drugs and the LEDD. The same results were shown by PD patients treated with safinamide 50 mg and patients who started safinamide without switching from a previous MAOBI. PD patients with safinamide 100 mg and patients who started safinamide switching from a previous MAOBI significantly improved in time spent in OFF and LEDD. In conclusion, safinamide is safe and effective in improving motor complications in patients with idiopathic PD and can be considered a useful levodopa sparing strategy.

5 Article X-linked Parkinsonism with Intellectual Disability caused by novel mutations and somatic mosaicism in RAB39B gene. 2017

Ciammola, Andrea / Carrera, Paola / Di Fonzo, Alessio / Sassone, Jenny / Villa, Roberta / Poletti, Barbara / Ferrari, Maurizio / Girotti, Floriano / Monfrini, Edoardo / Buongarzone, Gabriele / Silani, Vincenzo / Cinnante, Claudia Maria / Mignogna, Maria Lidia / D'Adamo, Patrizia / Bonati, Maria Teresa. ·IRCCS Istituto Auxologico Italiano, Department of Neurology and Laboratory of Neuroscience, Milan, Italy. · IRCCS San Raffaele Scientific Institute, Division of Genetics and Cell Biology, Unit of Genomics for Human Disease Diagnosis, Milan, Italy; IRCCS San Raffaele Scientific Institute Laboratory of Clinical Molecular Biology, Milan, Italy. · IRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico, Dino Ferrari Center, Neuroscience Section, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy; Dino Ferrari Center, Neuroscience Section, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy. · San Raffaele Scientific Institute and Vita-Salute University, Milan, Italy. · Clinic of Medical Genetics, IRCCS Istituto Auxologico Italiano, Milan, Italy. · IRCCS San Raffaele Scientific Institute Laboratory of Clinical Molecular Biology, Milan, Italy; Vita-Salute San Raffaele University, Chair of Clinical Pathology, Milan, Italy. · IRCCS Istituto Auxologico Italiano, Department of Neurology and Laboratory of Neuroscience, Milan, Italy; Dino Ferrari Center, Neuroscience Section, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy. · Neuroradiology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. · Molecular Genetics of Intellectual Disabilities Unit, Division of Neuroscience at IRCCS San Raffaele Scientific Institute, Milan, Italy. · Clinic of Medical Genetics, IRCCS Istituto Auxologico Italiano, Milan, Italy. Electronic address: mt.bonati@auxologico.it. ·Parkinsonism Relat Disord · Pubmed #28851564.

ABSTRACT: BACKGROUND: RAB39B pathogenic variants cause X-linked Parkinsonism associated with Intellectual Disability, known as Waisman syndrome, a very rare disorder that has been mainly identified through exome sequencing in large Parkinson's disease cohorts. In this study we searched for pathogenic variants in RAB39B in two Italian families affected by X-linked early-onset Parkinsonism and Intellectual Disability. METHODS: Three patients received neurological evaluation and underwent RAB39B sequencing. RESULTS: Two novel RAB39B frameshift variants were found to result in the absence of RAB39B protein (family 1: c.137dupT; family 2: c.371delA). Patients showed unilateral rest tremor and bradykinesia; one of them also displayed an early-onset postural tremor. Paramagnetic substance deposition in the substantia nigra, globus pallidi, red nucleus, putamen and pulvinar was assessed by brain imaging. Two patients also showed moderate calcification of globus pallidi. CONCLUSION: In this study we highlight the evidence that X-linked early-onset Parkinsonism associated with Intellectual Disability occurs as a pattern of clinical and neuroimaging features attributable to RAB39B pathogenic variants.

6 Article The role of TREM2 R47H as a risk factor for Alzheimer's disease, frontotemporal lobar degeneration, amyotrophic lateral sclerosis, and Parkinson's disease. 2015

Lill, Christina M / Rengmark, Aina / Pihlstrøm, Lasse / Fogh, Isabella / Shatunov, Aleksey / Sleiman, Patrick M / Wang, Li-San / Liu, Tian / Lassen, Christina F / Meissner, Esther / Alexopoulos, Panos / Calvo, Andrea / Chio, Adriano / Dizdar, Nil / Faltraco, Frank / Forsgren, Lars / Kirchheiner, Julia / Kurz, Alexander / Larsen, Jan P / Liebsch, Maria / Linder, Jan / Morrison, Karen E / Nissbrandt, Hans / Otto, Markus / Pahnke, Jens / Partch, Amanda / Restagno, Gabriella / Rujescu, Dan / Schnack, Cathrin / Shaw, Christopher E / Shaw, Pamela J / Tumani, Hayrettin / Tysnes, Ole-Bjørn / Valladares, Otto / Silani, Vincenzo / van den Berg, Leonard H / van Rheenen, Wouter / Veldink, Jan H / Lindenberger, Ulman / Steinhagen-Thiessen, Elisabeth / Anonymous8670828 / Teipel, Stefan / Perneczky, Robert / Hakonarson, Hakon / Hampel, Harald / von Arnim, Christine A F / Olsen, Jørgen H / Van Deerlin, Vivianna M / Al-Chalabi, Ammar / Toft, Mathias / Ritz, Beate / Bertram, Lars. ·Platform for Genome Analytics, Institutes of Neurogenetics & Integrative and Experimental Genomics, University of Lübeck, Lübeck, Germany; Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany. Electronic address: christina.lill@gmx.de. · Department of Neurology, Oslo University Hospital, Oslo, Norway. · Department of Clinical Neuroscience, Institute of Psychiatry, King's College London, London, UK. · Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, PA, USA; Division of Human Genetics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, PA, USA; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. · Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. · Max Planck Institute for Human Development, Berlin, Germany. · Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark. · Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany. · Department of Psychiatry and Psychotherapy, Technische Universität München, Munich, Germany. · Rita Levi Montalcini Department of Neuroscience, ALS Center, University of Torino, Torino, Italy. · Rita Levi Montalcini Department of Neuroscience, ALS Center, University of Torino, Torino, Italy; Neuroscience Institute of Turin, Turin, Italy. · Department of Neurology, Linköping University, Linköping, Sweden. · Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, Goethe University of Frankfurt, Frankfurt, Germany. · Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden. · Department of Neurology, University of Ulm, Ulm, Germany. · The Norwegian Centre for Movement Disorders, Stavanger University Hospital, Stavanger, Norway. · School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK; Neurosciences Division, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK. · Department of Pharmacology, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden. · Department of Neuro-/Pathology, University of Oslo and Oslo University Hospital, Oslo, Norway; Lübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany. · Department of Clinical Pathology, Molecular Genetics Unit, Azienda Ospedaliera Città della Salute e della Scienza, Torino, Italy. · Department of Psychiatry, University of Halle-Wittenberg, Halle, Germany. · Department of Neuroscience, Sheffield Institute for Translational Neuroscience (SITraN), Faculty of Medicine, Dentistry and Health, University of Sheffield, Sheffield, UK. · Department of Neurology, Haukeland University Hospital, Bergen, Norway; Department of Clinical Medicine, University of Bergen, Bergen, Norway. · Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milano, Italy; Department of Pathophysiology and Tranplantation, "Dino Ferrari" Center, Università degli Studi di Milano, Milano, Italy. · Department of Neurology, Neuromuscular Diseases Brain Center Rudolf Magnus, Netherlands ALS Center, University Medical Center Utrecht, Utrecht, The Netherlands. · Interdisciplinary Metabolic Center, Lipids Clinic, Charité University Medicine, Berlin, Germany. · German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany; Department of Psychosomatic Medicine, University of Rostock, Rostock, Germany. · Department of Psychiatry and Psychotherapy, Technische Universität München, Munich, Germany; Neuroepidemiology and Ageing Research Unit, School of Public Health, Faculty of Medicine, The Imperial College of Science, Technology, and Medicine, London, UK; West London Cognitive Disorders Treatment and Research Unit, West London Mental Health Trust, London, UK. · AXA Research Fund & UPMC Chair, Paris, France; Département de Neurologie, Sorbonne Universités, Université Pierre et Marie Curie, Institut de la Mémoire et de la Maladie d'Alzheimer & Institut du Cerveau et de la Moelle épinière (ICM), Hôpital de la Pitié-Salpétrière, Paris, France. · Department of Epidemiology and Environmental Sciences, School of Public Health, University of California, Los Angeles, CA, USA. · Platform for Genome Analytics, Institutes of Neurogenetics & Integrative and Experimental Genomics, University of Lübeck, Lübeck, Germany; Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany; Neuroepidemiology and Ageing Research Unit, School of Public Health, Faculty of Medicine, The Imperial College of Science, Technology, and Medicine, London, UK. ·Alzheimers Dement · Pubmed #25936935.

ABSTRACT: A rare variant in TREM2 (p.R47H, rs75932628) was recently reported to increase the risk of Alzheimer's disease (AD) and, subsequently, other neurodegenerative diseases, i.e. frontotemporal lobar degeneration (FTLD), amyotrophic lateral sclerosis (ALS), and Parkinson's disease (PD). Here we comprehensively assessed TREM2 rs75932628 for association with these diseases in a total of 19,940 previously untyped subjects of European descent. These data were combined with those from 28 published data sets by meta-analysis. Furthermore, we tested whether rs75932628 shows association with amyloid beta (Aβ42) and total-tau protein levels in the cerebrospinal fluid (CSF) of 828 individuals with AD or mild cognitive impairment. Our data show that rs75932628 is highly significantly associated with the risk of AD across 24,086 AD cases and 148,993 controls of European descent (odds ratio or OR = 2.71, P = 4.67 × 10(-25)). No consistent evidence for association was found between this marker and the risk of FTLD (OR = 2.24, P = .0113 across 2673 cases/9283 controls), PD (OR = 1.36, P = .0767 across 8311 cases/79,938 controls) and ALS (OR = 1.41, P = .198 across 5544 cases/7072 controls). Furthermore, carriers of the rs75932628 risk allele showed significantly increased levels of CSF-total-tau (P = .0110) but not Aβ42 suggesting that TREM2's role in AD may involve tau dysfunction.

7 Article C9orf72 repeat expansions are restricted to the ALS-FTD spectrum. 2014

Ticozzi, Nicola / Tiloca, Cinzia / Calini, Daniela / Gagliardi, Stella / Altieri, Alessandra / Colombrita, Claudia / Cereda, Cristina / Ratti, Antonia / Pezzoli, Gianni / Borroni, Barbara / Goldwurm, Stefano / Padovani, Alessandro / Silani, Vincenzo. ·Department of Neurology and Laboratory of Neuroscience, Istituto di Ricovero e Cura a Carattere Scientifico Istituto Auxologico Italiano, Milan, Italy; Department of Pathophysiology and Transplantation, Dino Ferrari Center, Università degli Studi di Milano, Milan, Italy. Electronic address: n.ticozzi@auxologico.it. · Department of Neurology and Laboratory of Neuroscience, Istituto di Ricovero e Cura a Carattere Scientifico Istituto Auxologico Italiano, Milan, Italy; Doctoral School in Molecular Medicine, Department of Sciences and Biomedical Technologies, University of Milan, Milan, Italy. · Department of Neurology and Laboratory of Neuroscience, Istituto di Ricovero e Cura a Carattere Scientifico Istituto Auxologico Italiano, Milan, Italy. · Laboratory of Experimental Neurology, Istituto di Ricovero e Cura a Carattere Scientifico C. Mondino National Neurological Institute, Pavia, Italy. · Department of Neurology and Laboratory of Neuroscience, Istituto di Ricovero e Cura a Carattere Scientifico Istituto Auxologico Italiano, Milan, Italy; Department of Pathophysiology and Transplantation, Dino Ferrari Center, Università degli Studi di Milano, Milan, Italy. · Parkinson Institute, Istituti Clinici di Perfezionamento, Milan, Italy. · Centre for Neurodegenerative Disorders, University of Brescia, Brescia, Italy. ·Neurobiol Aging · Pubmed #24169076.

ABSTRACT: Expansion of a GGGGCC repeat (RE) in the C9orf72 gene has been recently reported as the main genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Given the growing evidence of genetic and clinicopathologic overlap among ALS, FTD, and other neurodegenerative diseases, we investigated the occurrence of RE in a subset of 9 patients with ALS-plus syndromes, including Parkinson's disease (PD), progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), and multiple system atrophy. We identified RE in 2 ALS-plus individuals (22.2%) displaying PSP and CBS features. On the basis of this finding, we extended our analysis to a cohort composed of 190 PD, 103 CBS, 107 PSP, and 177 Alzheimer's disease cases. We did not identify any RE in these patients, indicating that C9orf72 is in all probability not involved in the pathogenesis of these disorders. However, the high frequency of C9orf72 RE in patients with ALS-plus syndromes suggests that, similar to ALS-FTD patients, individuals with combined motor neuron and extrapyramidal features should be screened for RE, independent of their family history.

8 Article Noninvasive near-infrared live imaging of human adult mesenchymal stem cells transplanted in a rodent model of Parkinson's disease. 2012

Bossolasco, P / Cova, L / Levandis, G / Diana, V / Cerri, S / Lambertenghi Deliliers, G / Polli, E / Silani, V / Blandini, F / Armentero, M T. ·Fondazione Matarelli, Dipartimento di Farmacologia, Chemioterapia e Tossicologia Medica, Università degli Studi di Milano, Milan, Italy. ·Int J Nanomedicine · Pubmed #22334776.

ABSTRACT: BACKGROUND: We have previously shown that human mesenchymal stem cells (hMSCs) can reduce toxin-induced neurodegeneration in a well characterized rodent model of Parkinson's disease. However, the precise mechanisms, optimal cell concentration required for neuroprotection, and detailed cell tracking need to be defined. We exploited a near-infrared imaging platform to perform noninvasive tracing following transplantation of tagged hMSCs in live parkinsonian rats. METHODS: hMSCs were labeled both with a membrane intercalating dye, emitting in the near- infrared 815 nm spectrum, and the nuclear counterstain, Hoechst 33258. Effects of near-infrared dye on cell metabolism and proliferation were extensively evaluated in vitro. Tagged hMSCs were then administered to parkinsonian rats bearing a 6-hydroxydopamine-induced lesion of the nigrostriatal pathway, via two alternative routes, ie, intrastriatal or intranasal, and the cells were tracked in vivo and ex vivo using near-infrared technology. RESULTS: In vitro, NIR815 staining was stable in long-term hMSC cultures and did not interfere with cell metabolism or proliferation. A significant near-infrared signal was detectable in vivo, confined around the injection site for up to 14 days after intrastriatal transplantation. Conversely, following intranasal delivery, a strong near-infrared signal was immediately visible, but rapidly faded and was completely lost within 1 hour. After sacrifice, imaging data were confirmed by presence/absence of the Hoechst signal ex vivo in coronal brain sections. Semiquantitative analysis and precise localization of transplanted hMSCs were further performed ex vivo using near-infrared imaging. CONCLUSION: Near-infrared technology allowed longitudinal detection of fluorescent-tagged cells in living animals giving immediate information on how different delivery routes affect cell distribution in the brain. Near-infrared imaging represents a valuable tool to evaluate multiple outcomes of transplanted cells, including their survival, localization, and migration over time within the host brain. This procedure considerably reduces the number of animal experiments needed, as well as interindividual variability, and may favor the development of efficient therapeutic strategies promptly applicable to patients.

9 Article Neuroprotective effects of human mesenchymal stem cells on neural cultures exposed to 6-hydroxydopamine: implications for reparative therapy in Parkinson's disease. 2012

Cova, Lidia / Bossolasco, Patrizia / Armentero, Marie-Therese / Diana, Valentina / Zennaro, Eleonora / Mellone, Manuela / Calzarossa, Cinzia / Cerri, Silvia / Deliliers, Giorgio Lambertenghi / Polli, Elio / Blandini, Fabio / Silani, Vincenzo. ·Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano 20149, Milan, Italy. l.cova@auxologico.it ·Apoptosis · Pubmed #22160861.

ABSTRACT: Stem cell (SC) transplantation represents a promising tool to treat neurodegenerative disorders, such as Parkinson's disease (PD), but positive therapeutic outcomes require elucidation of the biological mechanisms involved. Therefore, we investigated human Mesenchymal SCs (hMSCs) ability to protect murine differentiated Neural SCs (mdNSCs) against the cytotoxic effects of 6-hydroxydopamine (6-OHDA) in a co-culture model mimicking the in vivo neurovascular niche. The internalization of 6-OHDA mainly relies on its uptake by the dopamine active transporter (DAT), but its toxicity could also involve other pathways. We demonstrated that mdNSCs consistently expressed DAT along the differentiative process. Exposure to 6-OHDA did not affect hMSCs, but induced DAT-independent apoptosis in mdNSCs with generation of reactive oxygen species and caspases 3/7 activation. The potential neuroprotective action of hMSCs on mdNSCs exposed to 6-OHDA was tested in different co-culture conditions, in which hMSCs were added to mdNSCs prior to, simultaneously, or after 6-OHDA treatment. In the presence of the neurotoxin, the majority of mdNSCs acquired an apoptotic phenotype, while co-cultures with hMSCs significantly increased their survival (up to 70%) in all conditions. Multiplex human angiogenic array analysis on the conditioned media demonstrated that cytokine release by hMSCs was finely modulated. Moreover, sole growth factor addition yielded a similar neuroprotective effect on mdNSCs. In conclusion, our findings demonstrate that hMSCs protect mdNSCs against 6-OHDA neurotoxicity, and rescue cells from ongoing neurodegeneration likely through the release of multiple cytokines. Our findings provide novel insights for the development of therapeutic strategies designed to counteract the neurodegenerative processes of PD.