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Parkinson disease treatment

Yong Wang, Ge-Juan Zhang, Yi-Na Sun, Lu Yao, Hui-Sheng Wang, Cheng-Xue Du, Li Zhang, Jian Liu
L-DOPA-induced dyskinesia (LID) is a frequent complication of chronic L-DOPA therapy in the clinical treatment of Parkinson's disease (PD). The pathogenesis of LID involves complex molecular mechanisms in the striatum. Metabolomics can shed light on striatal metabolic alterations in LID. In the present study, we compared metabolomics profiles of striatum tissue from Parkinsonian rats with or without dyskinetic symptoms after chronic L-DOPA administration. A liquid chromatography-mass spectrometry based global metabolomics method combined with multivariate statistical analyses were used to detect candidate metabolites associated with LID...
March 15, 2018: Behavioural Brain Research
Toscane C Noordhoff, Jan Groen, Jeroen R Scheepe, Bertil F M Blok
CONTEXT: Surgical treatment of anatomic bladder outlet obstruction (BOO) may be indicated in males with neurogenic bladder dysfunction. A bothersome complication after surgery is urinary incontinence. OBJECTIVE: To identify the optimal practice in the surgical treatment of anatomic BOO in males with neurogenic bladder dysfunction, due to multiple sclerosis, Parkinson disease, spinal cord injury (SCI), spina bifida, or cerebrovascular accident (CVA). EVIDENCE ACQUISITION: A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement...
March 15, 2018: European Urology Focus
Gaetano Barbagallo, Rita Nisticò, Basilio Vescio, Antonio Cerasa, Giuseppe Olivadese, Salvatore Nigro, Marianna Crasà, Andrea Quattrone, Maria Giovanna Bianco, Maurizio Morelli, Antonio Augimeri, Maria Salsone, Fabiana Novellino, Giuseppe Nicoletti, Gennarina Arabia, Aldo Quattrone
INTRODUCTION: The aim of our study was to investigate the effect of apomorphine and placebo on resting tremor in tremor-dominant Parkinson's disease (tPD) patients. METHODS: Fifteen tPD patients were enrolled. Each patient underwent two treatments on two consecutive days: on day one the patients received a subcutaneous injection of placebo, while on day two they received apomorphine. On each day, the patients underwent three electrophysiological recording sessions: T0, T1, and T2: before, 30 min, and 60 min after the treatment respectively...
March 14, 2018: Parkinsonism & related Disorders
Susanna Nuvoli, Barbara Palumbo, Simona Malaspina, Giuseppe Madeddu, Angela Spanu
Nuclear medicine procedures are widely used as "in vivo" biomarkers in a large number of brain diseases, especially in the diagnosis of Parkinson's disease (PD) and of parkinsonian disorders (pD). Furthermore, nuclear medicine is used in the differential diagnosis of dementias especially Alzheimer's disease (AD) and dementia with Lewy's bodies (LBD) which share many clinical symptoms and often LBD is misdiagnosed as AD. The differential diagnosis between these clinical entities is crucial for treatment since LBD also shares some clinical symptoms with parkinsonian disorders...
March 20, 2018: Hellenic Journal of Nuclear Medicine
Moran Gilat, Ana Lígia Silva de Lima, Bastiaan R Bloem, James M Shine, Jorik Nonnekes, Simon J G Lewis
Freezing of gait is a devastating symptom of Parkinson's disease and other forms of parkinsonism. It poses a major burden on both patients and their families, as freezing often leads to falls, fall-related injuries and a loss of independence. Treating freezing of gait is difficult for a variety of reasons: it has a paroxysmal and unpredictable nature; a multifaceted pathophysiology, with an interplay between motor elements (disturbed stepping mechanisms) and non-motor elements (cognitive decline, anxiety); and a complex (and likely heterogeneous) underlying neural substrate, involving multiple failing neural networks...
March 12, 2018: Parkinsonism & related Disorders
Rui-Fang Wang, Guo-Fang Xue, Christian Hölscher, Miao-Jing Tian, Peng Feng, Ji-Ying Zheng, Dong-Fang Li
Glucagon-like peptide-1(GLP-1) is a growth factor that has neuroprotective and anti-inflammatory properties. The protease resistant GLP-1 analogue liraglutide has been shown to be neuroprotective in previous studies in animal models of Alzheimer's disease or Parkinson's disease. Status epilepticus (SE) is a complex disorder, involving many underlying pathological processes, including excitotoxic and chronic inflammatory events. The present pilot study aims to investigate whether liraglutide alleviates the chronic inflammation response and mitochondrial stress induced by SE in the lithium-pilocarpine animal model...
March 9, 2018: Epilepsy Research
Chye Soi Moi, Chia Kin Yen, Khuen Yen Ng, Koh Rhun Yian
Protein misfolding and aggregation have been considered the common pathological hallmarks for a number of neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD). These abnormal proteins aggregation damage mitochondria and induce oxidative stress and resulting neuronal cell death. Prolong neuronal damage activates microglia and astrocytes, development of inflammation reaction and further promotes neurodegeneration. Thus, elimination of abnormal proteins aggregation without eliciting any adverse effects are the main treatment strategies...
March 15, 2018: CNS & Neurological Disorders Drug Targets
Manon Auffret, Sophie Drapier, Marc Vérin
Apomorphine is now recognized as the oldest antiparkinsonian drug on the market. Though still underused, it is increasingly prescribed in Europe for patients with advanced Parkinson's disease (PD) with motor fluctuations. However, its history is far from being limited to movement disorders. This paper traces the history of apomorphine, from its earliest empirical use, to its synthesis, pharmacological development, and numerous indications in human and veterinary medicine, in light of its most recent uses and newest challenges...
March 15, 2018: Drugs in R&D
Paola Imbriani, Tommaso Schirinzi, Maria Meringolo, Nicola B Mercuri, Antonio Pisani
Significant advances have been made in the understanding of the numerous mechanisms involved in Parkinson's disease (PD) pathogenesis. The identification of PD pathogenic mutations and the use of different animal models have contributed to better elucidate the processes underlying the disease. Here, we report a brief survey of some relevant cellular mechanisms, including autophagic-lysosomal dysfunction, endoplasmic reticulum stress, and mitochondrial impairment, with the main aim to focus on their potential convergent roles in determining early alterations at the synaptic level, mainly consisting in a decrease in dopamine release at nigrostriatal terminals and loss of synaptic plasticity at corticostriatal synapses...
2018: Frontiers in Neurology
Lívia H Morais, Daniela B Hara, Maíra A Bicca, Anicleto Poli, Reinaldo N Takahashi
The factors that trigger the pathophysiology of Parkinson's disease (PD) are unknown. However, it is suggested that environmental factors, such as exposure to pesticides, play an important role, in addition to genetic predisposition and aging. Early signs of PD can appear in the gastrointestinal (GI) tract and in the olfactory system, preceding the onset of motor impairments by many years. The present study assessed the effects of oral rotenone administration (30 mg/kg) in inducing GI and olfactory dysfunctions associated with PD in mice...
April 2018: Behavioural Pharmacology
Carlo Cattaneo, Jaime Kulisevsky, Viviana Tubazio, Paola Castellani
INTRODUCTION: Chronic pain is an important yet overlooked non-motor symptom of Parkinson's disease (PD), caused by an imbalance of the dopaminergic and glutamatergic systems. Safinamide has a multimodal mechanism of action, dopaminergic (reversible MAO-B inhibition) and non-dopaminergic (modulation of the abnormal glutamate release), that might be beneficial for both motor and non-motor symptoms. OBJECTIVES: To investigate the long-term (2-year) efficacy of safinamide on PD chronic pain and to confirm the positive effects observed after 6 months of treatment...
March 14, 2018: Advances in Therapy
Maria Perez Carrion, Francesca Pischedda, Alice Biosa, Isabella Russo, Letizia Straniero, Laura Civiero, Marianna Guida, Christian J Gloeckner, Nicola Ticozzi, Cinzia Tiloca, Claudio Mariani, Gianni Pezzoli, Stefano Duga, Irene Pichler, Lifeng Pan, John E Landers, Elisa Greggio, Michael W Hess, Stefano Goldwurm, Giovanni Piccoli
Mutations in leucine-rich repeat kinase 2 gene ( LRRK2 ) are associated with familial and sporadic Parkinson's disease (PD). LRRK2 is a complex protein that consists of multiple domains, including 13 putative armadillo-type repeats at the N-terminus. In this study, we analyzed the functional and molecular consequences of a novel variant, E193K, identified in an Italian family. E193K substitution does not influence LRRK2 kinase activity. Instead it affects LRRK2 biochemical properties, such as phosphorylation at Ser935 and affinity for 14-3-3ε...
2018: Frontiers in Molecular Neuroscience
Ren-Hong Du, Hong-Bin Sun, Zhao-Li Hu, Ming Lu, Jian-Hua Ding, Gang Hu
Classical activation (M1 phenotype) and alternative activation (M2 phenotype) are the two polars of microglial activation states that can produce either neurotoxic or neuroprotective effects in the immune pathogenesis of Parkinson's disease (PD). Exploiting the beneficial properties of microglia cells by modulating their polarization states provides great potential for the treatment of PD. However, the mechanism that regulates microglia polarization remains elusive. Here we demonstrated that Kir6.1-containing ATP-sensitive potassium (Kir6...
March 14, 2018: Cell Death & Disease
Julie A Reisz, Alexander S Barrett, Travis Nemkov, Kirk C Hansen, Angelo D'Alessandro
Proteins have been historically regarded as "nature's robots": Molecular machines that are essential to cellular/extracellular physical mechanical properties and catalyze key reactions for cell/system viability. However, these robots are kept in check by other protein-based machinery to preserve proteome integrity and stability. During aging, protein homeostasis is challenged by oxidation, decreased synthesis, and increasingly inefficient mechanisms responsible for repairing or degrading damaged proteins...
March 14, 2018: Expert Review of Proteomics
Anand Rughani, Jason M Schwalb, Christos Sidiropoulos, Julie Pilitsis, Adolfo Ramirez-Zamora, Jennifer A Sweet, Sandeep Mittal, Alberto J Espay, Jorge Gonzalez Martinez, Aviva Abosch, Emad Eskandar, Robert Gross, Ron Alterman, Clement Hamani
QUESTION 1: Is bilateral subthalamic nucleus deep brain stimulation (STN DBS) more, less, or as effective as bilateral globus pallidus internus deep brain stimulation (GPi DBS) in treating motor symptoms of Parkinson's disease, as measured by improvements in Unified Parkinson's Disease Rating Scale, part III (UPDRS-III) scores? RECOMMENDATION: Given that bilateral STN DBS is at least as effective as bilateral GPi DBS in treating motor symptoms of Parkinson's disease (as measured by improvements in UPDRS-III scores), consideration can be given to the selection of either target in patients undergoing surgery to treat motor symptoms...
March 12, 2018: Neurosurgery
Huiling Wang, Menglan Zhao, Jialong Chen, Yixian Ren, Guanghai Wang, Wenjun Li, Fei Zou
Parkinson's disease (PD) is one of the most debilitating neurodegenerative disorders. The etiology of sporadic PD remains unknown. One prominent hypothesis is that impaired mitochondrial function may underlie slow and progressive neurodegeneration. Mitochondrial calcium uniporter (MCU) is a crucial component that regulates the intramitochondrial Ca level. Ca uptake to the mitochondria by MCU, resulting in activation of mitochondrial dehydrogenases and stimulation of ATP synthesis, but excessive Ca uptake to the mitochondria resulting in cell apoptosis...
March 13, 2018: Neuroreport
Guangxin Chen, Juxiong Liu, Liqiang Jiang, Xin Ran, Dewei He, Yuhang Li, Bingxu Huang, Wei Wang, Dianfeng Liu, Shoupeng Fu
Neuroinflammation, characterized marked by microglial activation, plays a very important role in the pathogenesis of Parkinson's disease (PD). Upon activation, pro-inflammatory mediators are produced by microglia, triggering excessive inflammatory responses and ultimately damaging dopaminergic neurons. Therefore, the identification of agents that inhibit neuroinflammation may be an effective approach for developing novel treatments for PD. In this study, we sought to investigate whether peiminine protects dopaminergic neurons by inhibiting neuroinflammation...
March 12, 2018: International Journal of Molecular Sciences
Bhupinder Kumar, Mohit Kumar, Ashish Ranjan Dwivedi, Vinod Kumar
Monoamine oxidase B (MAO-B) inhibitors are potential drug candidates for the treatment of various neurological disorders including Parkinson's disease. A total of 20 new propargyl-containing 2,4,6-trisubstituted pyrimidine derivatives were synthesized and screened for MAO inhibition using Amplex Red assays. All the synthesized compounds were found to be reversible and selective inhibitors of the MAO-B isoform at sub-micromolar concentrations. MVB3 was the most potent MAO-B inhibitor with an IC50 value of 0...
March 13, 2018: ChemMedChem
Frederico Favaro Ribeiro, Francisco Jaime Bezerra Mendonca, Jahan B Ghasemi, Hamilton M Ishiki, Marcus Tullius Scotti, Luciana Scotti
Since antiquity, humanity has used medicinal plant preparations to cure its ills, and, as research has progressed, new technologies have enabled more investigations on natural compounds which originate from plants, fungi, and marine species. The health benefits that these natural products provide have become a motive for treatment studies of various diseases. Among them, the neurodegenerative diseases like Alzheimer's and Parkinson's, a major age-related neurodegenerative disorder. Studies with natural products for neurodegenerative diseases (particularly through molecular docking) search for, and then focus on those ligands which offer effective inhibition of the enzymes monoamine oxidase and acetylcholinesterase...
March 13, 2018: Combinatorial Chemistry & High Throughput Screening
Rodrigo Novaes Ferreira, Aline Silva de Miranda, Natalia Pessoa Rocha, Ana Cristina Simoes E Silva, Antonio Lucio Teixeira, Elizabeth Ribeiro da Silva Camargos
BACKGROUND: Parkinson´s Disease (PD) is a chronic, progressive condition, being the second most common neurodegenerative disorder worldwide. The classical features include: bradykinesia, resting tremor, rigidity and festination. These neurological alterations are probably due to the death of dopaminergic neurons in the substantia nigra pars compacta and consequent reduction of dopamine input into the striatum. The decrease of dopamine levels may also be involved in the emergence of non-motor symptoms, including cognitive impairment, anxiety and depression symptoms...
March 12, 2018: Current Medicinal Chemistry
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