2^nd International Conference on Parkinson’s Disease & Movement Disorders December 05-07, 2016 Phoenix, USA

Matteo Santoro successfully graduated in Chemistry and Pharmaceutical Technology at the University of Calabria, Italy in the year 2012. He is currently working on Parkinson’s disease and investigating the role or a protein called HMGB1 in the pathophysiology of the disease. During his PhD Matteo Santoro has received four different prizes for best PhD student poster presentation and talks at different conferences within and outside the University of Aberdeen. He successfully co-authored two peer reviewed research articles on Parkinson’s disease. The latest publication has seen him the main contributor of the study. He is presently a PhD student on the behavioral characterization of three different MPTP mouse models of Parkinson’s disease and investigating the role of acquired and innate immune system in Parkinson’s disease.

Mounting evidence suggests the involvement of the immune system in neurodegenerative disorders including Parkinson`s disease (PD). We recently reported increased levels of HMGB1 in PD patients as well as in the MPTP animal model of PD. In the present study we explored whether the release of HMGB1 in our mouse model of PD caused the activation of the NLRP3 (NOD-like Receptor Protein 3) positive inflammasome. NLRP3-inflammasome is a multiprotein complex, and part of the innate immune system that is activated in aseptic conditions such as tissue damage or metabolic impairment. Its activation leads ultimately to both formation and release of the proinflammatory cytokine IL-1β. C57BL6J mice were injected with the sub-acute regimen (30 mg/kg/day for five consecutive days i.p., control animals were injected with equivalent volume of saline solution) of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Brain tissue was harvested 1-2 days post-injection. Tissue was then prepared for double immunofluorescent staining of three different cell types: dopaminergic neurons, astrocytes and microglia, performed on midbrain sections inclusive of substantia nigra, or for western blotting experiments conducted on protein lysate from ventral midbrain. Our confocal microscopy analysis confirmed an increase in NLRP3 protein levels in the cytoplasm of microglia one day after MPTP injections. In parallel, heightened levels of the microglial MAC-1 protein were confirmed histologically at the level of the substantia nigra and by western blotting. This up-regulation of MAC-l, a surface receptor for HMGB1, may therefore constitute a critical link in the activation of cytoplasmic pathways leading to activation of the NLRP3-inflammasome in Parkinsonism.

Alan Wu is an intern student working in Dr. Bingwei Lu’s lab in Stanford University School of Medicine. He is currently a Junior in the Crystal Springs Uplands High School. This study is done with the instruction and guidance from his mentor, Dr. Zhihao Wu, who is a post-doc in Dr. Lu’s lab.

Recent studies suggest that moderate red wine consumption may confer several health benefits: longer lifespan, protection against heart diseases, certain cancers and age-related neurological diseases. These health benefits are believed to come from a compound called resveratrol. Here we investigate the potential effect of grape skin from pure merlot on Parkinson’s disease by incorporating grape skin powder into the daily food intake of Drosophila melanogaster with PINK1 loss-of-function. The benefits of consuming this grape skin powder have featured not only the improvement of indirect flight muscle functions, as shown in the rescue of abnormal wing posture in PINK1 mutant flies, but also prolonged the lifespan. The effect on WT flies’ life span is not significant. Mitochondrial dysfunction is linked to the pathogenesis of Parkinson’s disease, in particular, PINK1 has been suggested to interact with mitochondrial fusion/fission machinery and the autophagy pathway. To underscore the beneficial qualities of the grape skin, we further showed that consumption of the grape skin powder demonstrated a rescue of mitochondria aggregation phenotype in the muscle of PINK1 mutants. Moreover; results from western blots exhibited significantly elevated levels of LC3-II in the muscles of grape powder fed flies, indicating increased mitochondria autophagy. This effect is more obvious in flies fed with grape skin than the pure resveratrol compound. In addition, mutant flies appeared to be more sensitive than wild type flies. Our study suggested grape skin powder can induce autophagy activation, mediate the mitochondria function, and has potential protective benefit in a Parkinson's disease model.

Denisas Dankinas is a PhD student of Neurobiology and Biophysics Department of Vilnius University, Vilnius, Lithuania. He had participated in the number of international scientific conferences and had published 3 proceedings and 2 in a peer reviewed journal. At this moment he has 1 paper under review in reputed journal and one paper is also prepared for the publishing.

The beforehand preparation of movement is a highly important process, which increases the efficiency of movement execution. The disorder of movement preparation in schizophrenia patients was previously detected only with the help of electroencephalographic parameters, but not with the assessing of movement speed used in behavioral studies. It was recently found that appropriate preparation not only speeds up the movement, but also increases movement stability, which is measured with the intra-individual reaction time variability. Some studies also revealed that assessing of movement stability could detect the dysfunction of schizophrenia better than classical behavioral parameters. Hence, the main goal of this study was to verify if the parameter of movement stability could detect the impairment of movement preparation in schizophrenia patients. In order to achieve the main purpose, we carried out a study with 14 schizophrenia patients and 14 control group subjects. We used precueing task in our research, in which participants had to employ information about movement probability for its proper preparation. The main results showed that the impairment of movement preparation in schizophrenia patients was detected only with the movement stability measurement, although the movement speed failed to do so. Therefore, it was found that movement stability parameter has an appropriate sensitivity for detecting impaired movement preparation and could be employed in clinical studies.

Dr. Senderovich is a physician at Baycrest Health Science System with practice focused on Palliative Care, Pain Medicine and Geriatrics. She is an Assistant professor at the Department of Family and Community Medicine, and Division of Palliative Care at the University of Toronto who actively involved teaching medical students and residents. She has a broad international experience and a solid research background. Her research was accepted nationally and internationally. She is an author of multiple manuscripts focused on geriatrics, patient’s centered care, ethical and legal aspect of doctor patient relationship, palliative and end-of-life care.

Introduction There was an estimated 36.5 million individuals worldwide living with dementia in 2010 as per World Health Organization. In addition to deficits in cognitive domains, responsive behaviours in dementia (RBD) greatly impact the quality-of-life of individuals with dementia and greatly increase caregiver burden. Current treatment modalities are not always effective, and thus non-pharmacological approaches along with careful use of pharmacological therapies should be considered in the management of RBD. Therapeutic Touch (TT) is a simple procedure that only requires a pair of hands and a compassionate mind. TT allows for clear and respectful communication with the patient and helps to avoid confrontation by providing stimulation and structure. Objective To review the publications that evaluate the use of TT in the management of RBD. Methods We searched PubMed for ‘Therapeutic Touch’ and “Dementia’. We limited our inclusion to reviews and studies published in the last 10 years. We excluded articles in languages other than English and studies for which no outcomes were reported. Results Four of the five examined studies suggest that Therapeutic Touch reduces restless behaviours found in dementia. However, there are limitations to these studies including methodological variability and small sample sizes. Conclusions TT is garnering attention for its potential role in ameliorating RBD in patients suffering from different stages of dementia and many are looking into using TT in palliative care settings. It can be used in inpatient and outpatient settings. However, at this time, there is insufficient data and further studies need to be done before definite conclusions can be drawn.

Radek Vodicka obtained his degree in Biology from the Faculty of Science, Masaryk University, Brno, Czech Republic, specializing in Genetics and Molecular Biology. He joined the DNA laboratory of the Department of Medical Genetics and Foetal Medicine, the University Hospital, Olomouc, where he obtained a post-graduate qualification in the Laboratory Method of Medical Genetics (2002). He defended his PhD thesis ‘Y-chromosomal sequences in Turner syndrome patients’ in 2003 and habilitated in 2013. His main research and clinical interest is a quantitative analysis of Human DNA sequences in relation to genetic diseases, infertility and cancerogensis.

Parkinson's disease (PD) can be caused by genetic changes in a lot of genes. The effect of these changes is determined by the nature of the mutation and ranges from weak associations to pathogenic mutation which leads to loss of protein function. Our study is based on epidemiological data which show significantly increased prevalence of PD (2.9%) in an isolated population of south-eastern Moravia in the Czech Republic. We compared two different Next Generation Sequencing (NGS) data analysis approaches in DNA from 28 PD patients in the genes responsible for Parkinsonism (ADH1C, ATP13A2, EIF4G1, FBXO7, GBA + GBAP1, GIGYF2, HTRA2, LRRK2, MAPT, PARK2, PARK7, PINK1, PLA2G6, SNCA, UCHL1 and VPS35) using: 1) Already described missense rare variants or pathogenic mutations and 2) Twelve control DNA samples from the same isolated population. Ion Torrent NGS data processing and trimming from Fastaq through “bam” to “vcf” files was done parallel by Torrent Suite/Ion Reporter and NextGene software. Variants were than filtered using following parameters: AQ˃20; Read coverage ˃20; MAF˂0,01; SIFT: 0 - 0,05 and/or PolyPhen-2: 0,2 -1. After filtering out, three missense mutations were found in LRRK2 gene: rs33995883 in 6/0 patients/control (p/c), rs33958906 in 1/1p/c, rs781737269 in 3/0p/c, one missense mutation in MAPT gene rs63750072 in 6/1p/c and one mutation in HTRA2 gene rs72470545 in 3/1p/c. Both the results from NextGene with Ion Torrent adaptation and from Ion Reporter significantly correlated in variant calling. Our study may contribute to further explanation of genetic background of Parkinsonism.

Induction of the antioxidant enzyme hemeoxygenase-1 (HO-1) was observed in both astrocytes and neurons in the substantianigra of patients with Parkinson’s disease (PD). In the current study, we investigated whether HO-1 behaves differently between neurons and astrocytes under the condition of neurotoxicity related to PD. The results showed a time-dependent HO-1 upregulation in primary cultured ventral mesencephalon (VM) neurons and astrocytes treated with the mitochondria complex I inhibitor 1-methyl-4-phenylpyridinium (MPP+) or recombinant α-synuclein. However, HO-1 upregulation appeared much later in neurons than in astrocytes. The HO-1 inhibitor zinc protoporphyrin (ZnPP) aggravated MPP+- or α-synuclein-induced oxidative damage in both astrocytes and neurons, indicating that this HO-1 response was cytoprotective. For neurons, the HO-1 activator cobalt protoporphyrin IX (CoPPIX) exerted protective effects against MPP+ or α-synuclein during moderate HO-1 upregulation, but it aggravated damage at the peak of the HO-1 response. For astrocytes, CoPPIX always showed protective effects. Higher basal and CoPPIX-induced mitochondrial ferritin (MtFt) levels were detected in astrocytes. Lentivirus-mediated MtFt overexpression rescued the neuronal damage induced by CoPPIX, indicating that a large MtFt buffering capacity contributes to pronounced HO-1 tolerance in astrocytes. Such findings suggest that astrocyte-targeted HO-1 interventions have potential as a novel pharmacological treatment strategy in PD.

Induction of the antioxidant enzyme hemeoxygenase-1 (HO-1) was observed in both astrocytes and neurons in the substantianigra of patients with Parkinson’s disease (PD). In the current study, we investigated whether HO-1 behaves differently between neurons and astrocytes under the condition of neurotoxicity related to PD. The results showed a time-dependent HO-1 upregulation in primary cultured ventral mesencephalon (VM) neurons and astrocytes treated with the mitochondria complex I inhibitor 1-methyl-4-phenylpyridinium (MPP+) or recombinant α-synuclein. However, HO-1 upregulation appeared much later in neurons than in astrocytes. The HO-1 inhibitor zinc protoporphyrin (ZnPP) aggravated MPP+- or α-synuclein-induced oxidative damage in both astrocytes and neurons, indicating that this HO-1 response was cytoprotective. For neurons, the HO-1 activator cobalt protoporphyrin IX (CoPPIX) exerted protective effects against MPP+ or α-synuclein during moderate HO-1 upregulation, but it aggravated damage at the peak of the HO-1 response. For astrocytes, CoPPIX always showed protective effects. Higher basal and CoPPIX-induced mitochondrial ferritin (MtFt) levels were detected in astrocytes. Lentivirus-mediated MtFt overexpression rescued the neuronal damage induced by CoPPIX, indicating that a large MtFt buffering capacity contributes to pronounced HO-1 tolerance in astrocytes. Such findings suggest that astrocyte-targeted HO-1 interventions have potential as a novel pharmacological treatment strategy in PD.

Prabaharan Chellamuthu is currently doing his Neurology residency in Institute of Neurology, Madras Medical College, Chennai, India. He has done his under graduation from 2004-2010 in Stanley Medical college, Chennai. He has done MD Paediatrics from 2011-2014 at Lady Hardinge Medical College, New Delhi, India. He has received Dr. C.B. Rama Rao prize and N. Radhakrishna Iyer prize in Stanley Medical College. He has published paper on infantile spasms and presented posters in both national and international conferences. His areas of interest are paediatric epilepsies and movement disorders.

Dystonia is a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive, movements, postures, or both. The aim of the study is to present the profile of patients presenting with dystonia in a tertiary care center in southern India. The study period is from January, 2015 to June, 2016. Data of patients admitted in neurology ward or attending movement disorder clinic of Madras Medical College, Chennai, India were collected retrospectively and were analyzed. A total of 30 patients with dystonia were included in the study of which 43% (n=13) were males and the rest were females; 40% (n=12) patients had isolated dystonia while the remaining 60% (n=18) had combined dystonia syndromes. Based on the age of onset, 30% (n=9) patients had adolescent onset (13-20 yrs), 43% (n=13) had early adulthood onset (21-40 yrs) and 27% (n=8) had late adulthood onset (>40 yrs). Based on body distribution, 33% (n=10) patients had focal dystonia, 7% (n=2) had segmental, 47% (n=14) had multifocal dystonia, 7% (n=2) had hemidystonia and 7% (n=2) had generalized dystonia. Based on the etiology 47% (n=14) patients had degenerative cause [43% (n=13) cases had Wilson and 3% (n=1) had neuro acanthocytosis], 13% (n=4) patients had acquired cause [10% (n=3) cases were drug induced and 3% (n=1) due to hypoxic brain injury and in the remaining 40% (n=12) patients, no cause could be found. Based on the progression, 47% (n=14) patients had progressive disease and in the remaining patients the disease was static or recovered. Wilson’s disease is by far the common degenerative disease presenting with dystonia in our center & cervical dystonia is the most common idiopathic cause.