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Treatment of parkinson

Elkurd T Mazen, Laxman B Bahroo, Rajesh Pahwa
Levodopa is the most efficacious treatment for Parkinson's disease (PD). Long-term treatment with levodopa is limited due to dyskinesia. Dyskinesia in PD can be socially and functionally disabling. Extended-release amantadine (amantadine ER) is the first approved medication for the treatment of dyskinesia. When it is given at bedtime, it reaches plasma concentration approximately twice the level achieved by amantadine immediate release. Amantadine ER reduces the severity and duration of dyskinesia during the day, reduces OFF time and increases ON time without troublesome dyskinesia...
March 22, 2018: Neurodegenerative Disease Management
Yongping Chen, Bei Cao, Ruwei Ou, Qianqian Wei, Xueping Chen, Bi Zhao, Ying Wu, Wei Song, Hui-Fang Shang
Large-scale meta-analyses of genome-wide association studies have identified several loci linked to sporadic Parkinson's disease (PD). However, the roles of some important loci, such as HNMT Thr105Ile, STK39 rs2390669, and NMD3 rs34016896, have not been clarified in Chinese populations. Accumulating evidence indicates that some common clinicopathological characteristics are shared by different neurodegenerative diseases. Consequently, we conducted a large sample study to investigate associations between these variants and PD, multiple system atrophy (MSA), and amyotrophic lateral sclerosis (ALS) in Chinese populations...
March 21, 2018: Journal of Molecular Neuroscience: MN
Yunxia Zhang, Meiling Ge, Qiukui Hao, Birong Dong
The effects of induced pluripotent stem cells (iPSCs) in 6-hydroxydopamine-lesioned rat models of Parkinson's disease (PD) have been evaluated in multiple studies. However, the results evaluating the effectiveness of iPSCs in animal models of PD are mixed, primarily due to their low statistical power. In the current study, a meta-analysis was performed to describe the treatment effect of unsorted iPSCs on behavioral testing in experimental rat models of PD. Databases searched included PubMed, EMBASE, MEDLINE and the Cochrane Library from inception to March 2017...
March 2018: Biomedical Reports
Hiroshi Kataoka, Kazuma Sugie
Othello syndrome (OS) is a type of paranoid delusional jealousy, characterized by the false absolute certainty of the infidelity of a partner. Because OS has infrequently occurred in patients with Parkinson's disease (PD), the characteristics of OS in PD remain unclear. We reviewed the clinical characteristics of this syndrome in PD. We reviewed 67 patients who had PD with OS. OS was more common in men (45 patients) than in women (22 patients), and it frequently occurred in middle-aged patients. Until the onset of OS, the duration of PD (range, 2-19...
2018: Frontiers in Neurology
Guo Ge, Cang Chen, Michael James Guderyon, Jingwei Liu, Zhixu He, Yanni Yu, Robert A Clark, Senlin Li
Glial cell line-derived neurotrophic factor (GDNF) exhibits potent neuroprotective properties in preclinical models of Parkinson's disease (PD), but challenges in GDNF delivery have been reported from clinical trials. To address this barrier, we developed a hematopoietic stem cell transplantation (HSCT) -based macrophage-mediated GDNF therapy platform. Here we introduced a regulatable lentiviral vector (LV-MSP-Tet-Off-hGDNF) in order to allow the expression of human GDNF to be adjusted or stopped by oral administration of doxycycline (Dox)...
March 21, 2018: Stem Cells and Development
Josef Finsterer, Claudia Stollberger, Edmund Gatterer
This report describes a 66-year-old Caucasian male who acutely developed severe, bilateral impairment of visual acuity at 24 years of age. Leber's hereditary optic neuropathy (LHON) was suspected but the diagnosis was not genetically confirmed until the age of 49 years when the primary LHON mutation m.3460G>A was detected. Since onset, visual acuity had slightly improved. The family history was positive for LHON (brother, two sisters of mother, female cousin) and genetically confirmed in his brother and one aunt...
January 1, 2018: Journal of International Medical Research
María Figueiredo-González, Patricia Reboredo-Rodríguez, Carmen González-Barreiro, Alegría Carrasco-Pancorbo, Jesús Simal-Gándara, Beatriz Cancho-Grande
The increasing interest in the Mediterranean diet is based on the protective effects against several diseases, including neurodegenerative disorders. Polyphenol-rich functional foods have been proposed to be unique supplementary and nutraceutical treatments for these disorders. Extra-virgin olive oils (EVOOs) obtained from 'Brava' and 'Mansa', varieties recently identified from Galicia (northwestern Spain), were selected for in vitro screening to evaluate their capacity to inhibit key enzymes involved in Alzheimer's disease (AD) (acetylcholinesterase (AChE), butyrylcholinesterase (BuChE) and 5-lipoxygenase (5-LOX)), major depressive disorder (MDD) and Parkinson's disease (PD) (monoamine oxidases: h MAO-A and h MAO-B respectively)...
March 21, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Nesibe Peker, Vinay Donipadi, Mridula Sharma, Craig McFarlane, Ravi Kambadur
Parkinson's Disease is a neurodegenerative disease characterized by tremors, muscle stiffness and muscle weakness. Molecular genetic analysis confirmed that mutations in PARKIN and PINK1 genes, which play major roles in mitochondrial quality control and mitophagy, are frequently associated with Parkinson's Disease. PARKIN is an E3 ubiquitin ligase that translocates to mitochondria during loss of mitochondrial membrane potential to increase mitophagy. Although muscle dysfunction is noted in Parkinson's Disease, little is known about the involvement of PARKIN in the muscle phenotype of Parkinson's Disease...
March 21, 2018: American Journal of Physiology. Cell Physiology
Liang Ouyang, Lan Zhang, Shouyue Zhang, Dahong Yao, Yuqian Zhao, Guan Wang, Leilei Fu, Peng Lei, Bo Liu
UNC-51-like kinase 1 (ULK1), the yeast Atg1 ortholog, is the sole serine-threonine kinase and initiating enzyme in autophagy, which may be regarded as a target in Parkinson's disease (PD). Herein, we discovered a small molecule 33i (BL-918) as a potent activator of ULK1 by structure-based drug design. Subsequently, some key amino acid residues (Arg18, Lys50, Asn86 and Tyr89) were found to be crucial to the binding pocket between ULK1 and 33i by site-directed mutagenesis. Moreover, we found that 33i induced autophagy via the ULK complex in SH-SY5Y cells...
March 21, 2018: Journal of Medicinal Chemistry
Anna J Pedrosa Carrasco, Lars Timmermann, David J Pedrosa
A considerable body of research has recently emerged around nonmotor symptoms in Parkinson's disease (PD) and their substantial impact on patients' well-being. A prominent example is constipation which occurs in up to two thirds of all PD-patients thereby effecting psychological and social distress and consequently reducing quality of life. Despite the significant clinical relevance of constipation, unfortunately little knowledge exists on effective treatments. Therefore this systematic review aims at providing a synopsis on clinical effects and safety of available treatment options for constipation in PD...
2018: NPJ Parkinson's Disease
Dillon F Da Fonte, Chris J Martyniuk, Lei Xing, Vance L Trudeau
Radial glial cells (RGCs) are the main macroglia in the teleost brain and have established roles in neurogenesis and neurosteroidogenesis. They are the only brain cell type expressing aromatase B ( cyp19a1b ), the enzyme that synthesizes estrogens from androgen precursors. There are few studies on the regulation of RGC functions, but our previous investigations demonstrated that dopamine stimulates cyp19a1b expression in goldfish RGCs, while secretoneurin A (SNa) inhibits the expression of this enzyme. Here, we determine the range of proteins and cellular processes responsive to SNa treatments in these steroidogenic cells...
2018: Frontiers in Endocrinology
Martin Klietz, Amelie Tulke, Lars H Müschen, Lejla Paracka, Christoph Schrader, Dirk W Dressler, Florian Wegner
Background: Parkinson's disease (PD) is the second most frequent neurodegenerative disease of the elderly. Patients suffer from various motor and non-motor symptoms leading to reduced health-related quality of life (HRQOL) and an increased mortality. Their loss of autonomy due to dementia, psychosis, depression, motor impairments, falls, and swallowing deficits defines a phase when palliative care interventions might help to sustain or even improve quality of life. Objective: The aim of this study was to investigate the current status of palliative care implementation and quality of life in a local cohort of advanced PD patients in order to frame and improve future care...
2018: Frontiers in Neurology
Danielle E Mor, Harry Ischiropoulos
In Parkinson's disease (PD), the loss of dopamine-producing neurons in the substantia nigra (SN) leads to severe motor impairment, and pathological inclusions known as Lewy bodies contain aggregated α-synuclein protein. The relationship of α-synuclein aggregation and dopaminergic degeneration is unclear. This commentary highlights a recent study showing that the interaction of α-synuclein with dopamine may be an important mechanism underlying disease. Elevating dopamine levels in mice expressing human α-synuclein with the A53T familial PD mutation recapitulated key features of PD, including progressive neurodegeneration of the SN and decreased ambulation...
2018: Journal of Experimental Neuroscience
Yongchul Jang, Insu Kwon, Wankeun Song, Ludmila M Cosio-Lima, Youngil Lee
Parkinson's disease (PD) is a neurodegenerative disorder caused by loss of dopaminergic neurons in the substantia nigra, leading to motor dysfunction. Growing evidence has demonstrated that endurance exercise (EE) confers neuroprotection against PD; However, the exact molecular mechanisms responsible for exercise-induced protection of dopaminergic neurons in PD remain unclear. Since oxidative stress plays a key role in the degenerative process of PD. We investigated whether EE-induced neuroprotection is associated with enhanced antioxidative capacity and autophagy, using a mouse model of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration...
March 17, 2018: Neuroscience
Pennapa Chonpathompikunlert, Phetcharat Boonruamkaew, Wanida Sukketsiri, Pilaiwanwadee Hutamekalin, Morakot Sroyraya
BACKGROUND: Apium graveolens L. is a traditional Chinese medicine prescribed as a treatment for hypertension, gout, and diabetes. This study aimed to determine the neuroprotective effects of A. graveolens extract against a Parkinson's disease (PD) model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in C57BL/6 mice. METHODS: Male C57BL/6 mice treated with MPTP were orally dosed with A. graveolens extract daily for 21 days. Behavioral tests, including a rotarod apparatus, a narrow beam test, a drag test, a grid walk test, a swimming test, and a resting tremor evaluation, were performed...
March 20, 2018: BMC Complementary and Alternative Medicine
Sabato Santaniello, John T Gale, Sridevi V Sarma
Over the last 30 years, deep brain stimulation (DBS) has been used to treat chronic neurological diseases like dystonia, obsessive-compulsive disorders, essential tremor, Parkinson's disease, and more recently, dementias, depression, cognitive disorders, and epilepsy. Despite its wide use, DBS presents numerous challenges for both clinicians and engineers. One challenge is the design of novel, more efficient DBS therapies, which are hampered by the lack of complete understanding about the cellular mechanisms of therapeutic DBS...
March 20, 2018: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
Antonio Lopalco, Annalisa Cutrignelli, Nunzio Denora, Angela Lopedota, Massimo Franco, Valentino Laquintana
The transport of dopamine across the blood brain barrier represents a challenge for the management of Parkinson's disease. The employment of central nervous system targeted ligands functionalized nanocarriers could be a valid tactic to overcome this obstacle and avoid undesirable side effects. In this work, transferrin functionalized dopamine-loaded liposomes were made by a modified dehydration-rehydration technique from hydrogenated soy phosphatidylcoline, cholesterol and 1,2-stearoyl- sn -glycero-3-phosphoethanolamine- N -[carboxy(poly(ethylene glycol)-2000)]...
March 20, 2018: Nanomaterials
Maria Jose Catalan, Jose Antonio Molina-Arjona, Pablo Mir, Esther Cubo, Jose Matias Arbelo, Pablo Martinez-Martin
Impulse control behaviors are a frequent comorbidity for patients with Parkinson's disease (PD). The objective of the present study was to evaluate the effectiveness levodopa-carbidopa intestinal gel (LCIG) therapy on impulse control disorders (ICDs) in patients with advanced PD. We conducted a multicenter, observational, and prospective (6 months follow-up) study that included consecutive PD patients assigned to LCIG through routine medical practice. Patients completed visits at baseline, 1, 3, and 6 months after percutaneous endoscopic gastrostomy procedure...
March 20, 2018: Journal of Neurology
Shao-Hua Xu, Chao Yang, Wen-Biao Xian, Jing Gu, Jin-Long Liu, Lu-Lu Jiang, Jing Ye, Yan-Mei Liu, Qi-Yu Guo, Yi-Fan Zheng, Lei Wu, Wan-Ru Chen, Zhong Pei, Ling Chen
Deep brain stimulation of the subthalamic nucleus is recognized as the most effective treatment for moderate and advanced Parkinson's disease. Programming of the stimulation parameters is important for maintaining the efficacy of deep brain stimulation. Voltage is considered to be the most effective programming parameter. The present study is a retrospective analysis of six patients with Parkinson's disease (four men and two women, aged 37-65 years), who underwent bilateral deep brain stimulation of the subthalamic nucleus at the First Affiliated Hospital of Sun Yat-sen University, China, and who subsequently adjusted only the stimulation voltage...
February 2018: Neural Regeneration Research
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
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