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https://www.readbyqxmd.com/read/28323427/kinetin-riboside-and-its-protides-activate-the-parkinson-s-disease-associated-pten-induced-putative-kinase-1-pink1-independent-of-mitochondrial-depolarisation
#1
Laura Osgerby, Yu-Chiang Lai, Peter J Thornton, Joseph Amalfitano, Cécile S Le Duff, Iqra Jabeen, Hachemi Kadri, Ageo Miccoli, James H R Tucker, Miratul M K Muqit, Youcef Mehellou
Since loss of function mutations of PINK1 lead to early-onset Parkinson's disease, there has been growing interest in the discovery of small molecules that amplify the kinase activity of PINK1. We herein report the design, synthesis, serum stability and hydrolysis of four kinetin riboside ProTides. These ProTides, along with kinetin riboside, activated PINK1 in cells independent of mitochondrial depolarization. This highlights the potential of modified nucleosides and their phosphate prodrugs as treatments for neurodegenerative diseases...
March 21, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28320196/extended-timed-up-and-go-assessment-as-a-clinical-indicator-of-cognitive-state-in-parkinson-s-disease
#2
Tess Evans, Alexa Jefferson, Michelle Byrnes, Sue Walters, Soumya Ghosh, Frank L Mastaglia, Brian Power, Ryan S Anderton
OBJECTIVE: To evaluate a modified extended Timed Up and Go (extended-TUG) assessment against a panel of validated clinical assessments, as an indicator of Parkinson's disease (PD) severity and cognitive impairment. METHODS: Eighty-seven participants with idiopathic PD were sequentially recruited from a Movement Disorders Clinic. An extended-TUG assessment was employed which required participants to stand from a seated position, walk in a straight line for 7m, turn 180° and then return to the start, in a seated position...
April 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28319282/stereotactic-radiosurgery-for-essential-tremor-retrospective-analysis-of-a-19-year-experience
#3
Ajay Niranjan, Sudesh S Raju, Ali Kooshkabadi, Edward Monaco, John C Flickinger, L Dade Lunsford
BACKGROUND: Essential Tremor (ET) is a common movement disorder that can be disabling. Initial treatment is in the form of medical therapies. Patients with medically refractory ET seek surgical intervention which include radiofrequency thalamotomy, deep brain stimulation, and radiosurgical thalamotomy. Radiosurgical thalamotomy is a minimally invasive surgical option which is especially valuable for elderly and high surgical risk patients. OBJECTIVE: The purpose of this study was to retrospectively analyze the outcomes of stereotactic radiosurgery for patients suffering from medically refractory essential tremor...
March 20, 2017: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/28318827/measuring-the-benefits-of-using-market-based-approaches-to-provide-water-and-sanitation-in-humanitarian-contexts
#4
S Martin-Simpson, J Parkinson, E Katsou
The use of cash transfers and market based programming (CT/MBP) to increase the efficiency and effectiveness of emergency responses is gaining prominence in the humanitarian sector. However, there is a lack of existing indicators and methodologies to monitor activities designed to strengthen water and sanitation (WaSH) markets. Gender and vulnerability markers to measure the impact of such activities on different stakeholders is also missing. This study identifies parameters to monitor, evaluate and determine the added value of utilising CT/MBP to achieve WaSH objectives in humanitarian response...
March 16, 2017: Journal of Environmental Management
https://www.readbyqxmd.com/read/28316922/miracle-cells-for-natural-dentistry-a-review
#5
REVIEW
Rani Somani, Shipra Jaidka, Neeti Bajaj, Sameksha Arora
Stem cells are undifferentiated cells that can differentiate into specialized cells. Recently, enormous growth has been seen in the recognition of stem cell-based therapies, which have the potential to ameliorate the life of patients with conditions that span from Parkinson's disease to cardiac ischemia to bone or tooth loss. This research has produced new but unexplored possibilities in the regeneration of different organs and tissues. Presently, research is focused on the proficiency of stem cells and their utilization in dentistry, which is gaining interest...
January 2017: Journal of Oral Biology and Craniofacial Research
https://www.readbyqxmd.com/read/28314412/development-of-lrrk2-inhibitors-for-the-treatment-of-parkinson-s-disease
#6
K V Christensen, G P Smith, D S Williamson
Linkage and genome-wide association studies have identified a genetic risk locus for late-onset Parkinson's disease in chromosome 12, originally identified as PARK6. The causative gene was identified to code for a large multifunctional protein, LRRK2 (leucine-rich repeat kinase 2). The combined genetic and biochemical evidence supports a hypothesis in which the LRRK2 kinase function is causally involved in the pathogenesis of sporadic and familial forms of PD, and therefore that LRRK2 kinase inhibitors could be useful for treatment...
2017: Progress in Medicinal Chemistry
https://www.readbyqxmd.com/read/28303913/multiple-system-atrophy-insights-into-a-rare-and-debilitating-movement-disorder
#7
REVIEW
Florian Krismer, Gregor K Wenning
Multiple system atrophy (MSA) is a devastating and fatal neurodegenerative disorder. The clinical presentation of this disease is highly variable, with parkinsonism, cerebellar ataxia and autonomic failure being the most common - and often debilitating - symptoms. These symptoms progress rapidly, and patients die from MSA-related complications after 9 years of symptom duration on average. Unfortunately, the course of the disease cannot be improved by drug or surgical treatment. In addition, symptomatic treatment options are currently limited, and therapeutic benefits are often only transient...
March 17, 2017: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/28303260/evidence-for-an-additive-neurorestorative-effect-of-simultaneously-administered-cdnf-and-gdnf-in-hemiparkinsonian-rats-implications-for-different-mechanism-of-action
#8
Merja H Voutilainen, Francesca De Lorenzo, Polina Stepanova, Susanne Bäck, Li-Ying Yu, Päivi Lindholm, Eeva Pörsti, Mart Saarma, Pekka T Männistö, Raimo K Tuominen
Parkinson's disease (PD) is a neurodegenerative disorder associated with a progressive loss of dopaminergic (DAergic) neurons of the substantia nigra (SN) and the accumulation of intracellular inclusions containing α-synuclein. Current therapies do not stop the progression of the disease, and the efficacy of these treatments wanes over time. Neurotrophic factors (NTFs) are naturally occurring proteins promoting the survival and differentiation of neurons and the maintenance of neuronal contacts. CDNF (cerebral dopamine NTF) and GDNF (glial cell line-derived NTF) are able to protect DAergic neurons against toxin-induced degeneration in experimental models of PD...
January 2017: ENeuro
https://www.readbyqxmd.com/read/28302480/comprehensive-investigation-of-aberrant-micrornas-expression-in-cells-culture-model-of-mncl2-induced-neurodegenerative-disease
#9
Rong He, Xiaoyun Xie, Linyue Lv, Yongqi Huang, Xianmin Xia, Xiaowu Chen, Lei Zhang
Manganese (Mn) is required in various human physiological processes. Excessive Mn exposure causes manganism, a progressive neurodegenerative disorder similar to idiopathic Parkinson's disease (IPD). However, the detailed mechanism of Mn-induced neurotoxicity is not yet fully understood. MicroRNAs (miRNAs) play important roles in gene expression regulation, and miRNA expression profile provides additional biological and prognostic information of diseases. In our study, RNA sequencing was performed to profile miRNAs in the SH-SY5Y cells following MnCl2 treatment...
March 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28302035/translational-multimodality-neuroimaging
#10
Sushil K Sharma
Recently high-resolution, noninvasive, multimodality in-vivo molecular imaging with PET, SPECT, CT and MRI, employing fusion algorithms has revolutionized personalized medicine. However, specific radiopharmaceuticals (RPs) for the accurate diagnosis and effective treatment of progressive neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, drug addiction, and other cognitive impairments still remain in developmental phase. Currently, multimodality fusion neuroimaging is utilized for the determination of: pharmacokinetics and pre-clinical development of radiopharmaceuticals (RPs); in-vivo monitoring of stem cell transplantation therapy; nicotinic acetylcholine receptors (nAChRs) investigations; and regional cerebral blood flow and glucose metabolism in cognitively-impaired subjects employing noninvasive microPET and nano-SPECT imaging...
March 15, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28301304/neuroprotective-and-therapeutic-effect-of-caffeine-on-the-rat-model-of-parkinson-s-disease-induced-by-rotenone
#11
Yasser A Khadrawy, Ahmed M Salem, Karima A El-Shamy, Emad K Ahmed, Nevein N Fadl, Eman N Hosny
The present study aimed to investigate the protective and therapeutic effects of caffeine on rotenone-induced rat model of Parkinson's disease (PD). Rats were divided into control, PD model induced by rotenone (1.5 mg/kg intraperitoneally (i.p.) for 45 days), protected group injected with caffeine (30 mg/kg, i.p.) and rotenone for 45 days (during the development of PD model), and treated group injected with caffeine (30 mg/kg, i.p.) for 45 days after induction of PD model. The data revealed a state of oxidative and nitrosative stress in the midbrain and the striatum of animal model of PD as indicated from the increased lipid peroxidation and nitric oxide levels and the decreased reduced glutathione level and activities of glutathione-S-transferase and superoxide dismutase...
September 3, 2017: Journal of Dietary Supplements
https://www.readbyqxmd.com/read/28300069/extracellular-%C3%AE-synuclein-induces-sphingosine-1-phosphate-receptor-subtype-1-uncoupled-from-inhibitory-g-protein-leaving-%C3%AE-arrestin-signal-intact
#12
Lifang Zhang, Taro Okada, Shaymaa Mohamed Mohamed Badawy, Chihoko Hirai, Taketoshi Kajimoto, Shun-Ichi Nakamura
Parkinson's disease (PD) is the second most common neurodegenerative disorder. The presence of α-synuclein (α-Syn)-positive intracytoplasmic inclusions, known as Lewy bodies, is the cytopathological hallmark of PD. Increasing bodies of evidence suggest that cell-to-cell transmission of α-Syn plays a role in the progression of PD. Although extracellular α-Syn is known to cause abnormal cell motility, the precise mechanism remains elusive. Here we show that impairment of platelet-derived growth factor-induced cell motility caused by extracellular α-Syn is mainly attributed to selective inhibition of sphingosine 1-phosphate (S1P) signalling...
March 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28299787/first-clinical-experience-with-levodopa-carbidopa-microtablets-in-parkinson-s-disease
#13
M Senek, M Hellström, J Albo, P Svenningsson, D Nyholm
BACKGROUND: Levodopa is the most effective symptomatic treatment throughout the course of Parkinson's disease, but as the disease progresses, there may be a need for individualized, fine-tuned treatments. AIM: To evaluate individualized levodopa/carbidopa dosing using microtablets dispensed with a dose dispenser, with respect to efficacy and usability as perceived by patients. METHODS: Patient records and dose dispenser reports from patients previously or currently treated with microtablets and a dose dispenser were reviewed, and a patient questionnaire concerning effect and usability was sent to patients...
March 15, 2017: Acta Neurologica Scandinavica
https://www.readbyqxmd.com/read/28298033/diffusion-tractography-imaging-guided-frameless-linear-accelerator-stereotactic-radiosurgical-thalamotomy-for-tremor-case-report
#14
Won Kim, Justin Sharim, Stephen Tenn, Tania Kaprealian, Yvette Bordelon, Nzhde Agazaryan, Nader Pouratian
Essential tremor and Parkinson's disease-associated tremor are extremely prevalent within the field of movement disorders. The ventral intermediate (VIM) nucleus of the thalamus has been commonly used as both a neuromodulatory and neuroablative target for the treatment of these forms of tremor. With both deep brain stimulation and Gamma Knife radiosurgery, there is an abundance of literature regarding the surgical planning, targeting, and outcomes of these methodologies. To date, there have been no reports of frameless, linear accelerator (LINAC)-based thalomotomies for tremor...
February 24, 2017: Journal of Neurosurgery
https://www.readbyqxmd.com/read/28298022/magnetic-resonance-guided-focused-ultrasound-thalamotomy-for-tremor-a-report-of-30-parkinson-s-disease-and-essential-tremor-cases
#15
Menashe Zaaroor, Alon Sinai, Dorith Goldsher, Ayelet Eran, Maria Nassar, Ilana Schlesinger
OBJECTIVE Thalamotomy of the ventral intermediate nucleus (VIM) is effective in alleviating medication-resistant tremor in patients with essential tremor (ET) and Parkinson's disease (PD). MR-guided focused ultrasound (MRgFUS) is an innovative technology that enables noninvasive thalamotomy via thermal ablation. METHODS Patients with severe medication-resistant tremor underwent unilateral VIM thalamotomy using MRgFUS. Effects on tremor were evaluated using the Clinical Rating Scale for Tremor (CRST) in patients with ET and by the motor part of the Unified Parkinson's Disease Rating Scale (UPDRS) in patients with PD and ET-PD (defined as patients with ET who developed PD many years later)...
February 24, 2017: Journal of Neurosurgery
https://www.readbyqxmd.com/read/28296742/pseudohypoparathyroidism-with-basal-ganglia-calcification-a-case-report-of-rare-cause-of-reversible-parkinsonism
#16
Cheng-Yuan Song, Zhen-Xiang Zhao, Wei Li, Cong-Cong Sun, Yi-Ming Liu
RATIONALE: Parkinsonism can be secondary to many internal diseases, in some certain conditions, it seems that the clinical manifestations of parkinsonism presenting reversible. We report a case of patient with parkinsonism secondary to pseudohypoparathyroidism, who improved markedly after the supplement of serum calcium. PATIENT CONCERNS AND DIAGNOSES: A 52-year-old woman with acute parkinsonism was diagnosed as pseudohypoparathyroidism after the conducting of brain computed tomography, laboratory examinations, and gene detection...
March 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28296351/a-high-resolution-tape-sensor-improves-the-accuracy-of-applied-pressure-profiles-during-lower-leg-bandaging%C3%A2-%C3%A2-results-from-a-study-using-a-fibre-optic-sensing-tape
#17
Luke A Parkinson, Malou van Zanten, Neil Piller, John W Arkwright
Compression bandaging is a mainstay practice in the treatment of conditions such as chronic wounds and lymphoedema. However, the ability of practitioners to measure bandage application to a desired pressure profile is difficult because of sensor limitations. We have used a novel fibre-optic-based, high-resolution sub-bandage pressure monitor to measure adherence to a target pressure gradient during compression bandaging. Participants of various experience (n = 46) were asked to bandage a lower-leg manikin to a gradient of 40 (ankle) to 20 mmHg (proximal calf) in both a blinded trial and subsequently with sensor feedback...
March 10, 2017: International Wound Journal
https://www.readbyqxmd.com/read/28295625/oral-ambroxol-increases-brain-glucocerebrosidase-activity-in-a-nonhuman-primate
#18
Anna Migdalska-Richards, Wai Kin D Ko, Qin Li, Erwan Bezard, Anthony H V Schapira
Mutations in the glucocerebrosidase 1 (GBA1) gene are related to both Parkinson disease (PD) and Gaucher disease (GD). In both cases, the condition is associated with deficiency of glucocerebrosidase (GCase), the enzyme encoded by GBA1. Ambroxol is a small molecule chaperone that has been shown in mice to cross the blood-brain barrier, increase GCase activity and reduce alpha-synuclein protein levels. In this study, we analyze the effect of ambroxol treatment on GCase activity in healthy nonhuman primates. We show that daily administration of ambroxol results in increased brain GCase activity...
March 12, 2017: Synapse
https://www.readbyqxmd.com/read/28294055/therapeutic-molecular-and-computational-aspects-of-novel-monoamine-oxidase-mao-inhibitors
#19
M Ramesh, Yussif M Dokurugu, Michael D Thompson, Mahmoud Soliman
Due to the limited number of MAOs inhibitors in the clinic and several research efforts are aimed at the discovery of novel MAOs inhibitors. At present, high specificity and a reversible mode of inhibition of MAO-A/B are cited as desirable traits in drug discovery process. This will help to reduce the probability of causing target disruption and may increase the duration of action. Most of the existing MAO inhibitors lead to side effects due to lack of affinity and selectivity. Therefore, there is an urgent need to design novel, potent, reversible and selective inhibitors for MAO-A/B...
March 10, 2017: Combinatorial Chemistry & High Throughput Screening
https://www.readbyqxmd.com/read/28293967/efficacy-of-rasagiline-for-the-treatment-of-parkinson-s-disease-an-updated-meta-analysis
#20
Ying Chang, Li-Bo Wang, Dan Li, Ke Lei, Song-Yan Liu
OBJECTIVE: Rasagiline is a second-generation potent selective inhibitor of monoamine oxidase-B. The aim of the study was to analyze the effectiveness of rasagiline in treatment of Parkinson's disease (PD), both as monotherapy and combination therapy. METHODS: Medline, Cochrane, EMBASE, and Google Scholar databases were searched until 9 March 2016 using the keywords: Rasagiline, Azilect, Parkinson's disease. Randomized controlled trials of patients with PD who were randomized to treatment with rasagiline or placebo were included...
March 15, 2017: Annals of Medicine
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