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https://www.readbyqxmd.com/read/28636179/discontinuation-and-non-publication-of-neurodegenerative-disease-trials-a-cross-sectional-analysis
#1
J D Stefaniak, T C H Lam, N E Sim, R Al-Shahi Salman, D P Breen
BACKGROUND AND PURPOSE: Trial discontinuation and non-publication represent major sources of research waste in clinical medicine. No previous studies have investigated non-dissemination bias in clinical trials of neurodegenerative diseases. METHODS: ClinicalTrials.gov was searched for all randomized, interventional, phase II-IV trials that were registered between 1 January 2000 and 31 December 2009 and included adults with Alzheimer's disease, motor neurone disease, multiple sclerosis or Parkinson's disease...
June 21, 2017: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
https://www.readbyqxmd.com/read/28636141/binocular-facilitation-of-cone-specific-visual-evoked-potentials-in-colour-deficiency
#2
Jeff Rabin, Andrew Kryder, Dan Lam
BACKGROUND: Neural compensatory mechanisms have been proposed, which preserve the binocular visual field in glaucoma, as well as cognition in Alzheimer's disease and motor function in Parkinson's disease. It is conceivable that comparable mechanisms operate to preserve function in congenital and/or dystrophic disease. In hereditary colour vision deficiency (CVD), we observed significant facilitation in the amplitude of the binocular cone-specific visual evoked potential (VEP) compared to the monocular amplitude for the cone type corresponding to the CVD...
June 21, 2017: Clinical & Experimental Optometry: Journal of the Australian Optometrical Association
https://www.readbyqxmd.com/read/28635875/-disturbances-of-gait-and-postural-stability-in-chronic-cerebral-ischemia
#3
N N Vakhnina, V V Zakharov
Disturbances of gait and postural stability are characteristic of the chronic progressive vascular lesion of the brain observed in moderate to severe stages of cerebrovascular disease. Disconnections between the prefrontal cortex, basal ganglia and cerebellum due to the damage of the white matter (vascular leukoencephalopathy) underlie disturbances of gait and postural stability (shorter stride length, wider gait). There are difficulties in starting with possible stoppings during the walking, waiting in front of small barriers as well as difficulties in concentration (e...
2017: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
https://www.readbyqxmd.com/read/28635873/-a-role-of-p-glycoprotein-in-neurology
#4
I V Chernykh, A V Shchulkin, E N Yakusheva, N M Popova
On the basis of the analysis of literature data, the authors show a role of P-glycoprotein in the pathogenesis, pharmacotherapy and a prophylaxis of neurologic diseases (Alzheimer's disease, Parkinson's disease, epilepsy, stroke).
2017: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
https://www.readbyqxmd.com/read/28635653/virtual-screening-against-phosphoglycerate-kinase-1-in-quest-of-novel-apoptosis-inhibitors
#5
Jie Xia, Bo Feng, Qianhang Shao, Yuhe Yuan, Xiang Simon Wang, Naihong Chen, Song Wu
Inhibition of apoptosis is a potential therapy to treat human diseases such as neurodegenerative disorders (e.g., Parkinson's disease), stroke, and sepsis. Due to the lack of druggable targets, it remains a major challenge to discover apoptosis inhibitors. The recent repositioning of a marketed drug (i.e., terazosin) as an anti-apoptotic agent uncovered a novel target (i.e., human phosphoglycerate kinase 1 (hPgk1)). In this study, we developed a virtual screening (VS) pipeline based on the X-ray structure of Pgk1/terazosin complex and applied it to a screening campaign for potential anti-apoptotic agents...
June 21, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28635509/induced-pluripotent-stem-cell-derived-dopaminergic-neurons-from-adult-common-marmoset-fibroblasts
#6
Scott C Vermilyea, Scott Guthrie, Michael Meyer, Kim Smuga-Otto, Katarina Braun, Sara Howden, James A Thomson, Su-Chun Zhang, Marina Emborg, Dr Thaddeus G Golos
The common marmoset monkey (Callithrix jacchus; Cj) is an advantageous nonhuman primate species for modeling age-related disorders, including Parkinson's disease, due to their shorter lifespan compared to macaques. Cj-derived induced pluripotent stem cells (Cj-iPSCs) from somatic cells are needed for in vitro disease modeling and testing regenerative medicine approaches. Here we report the development of a novel Cj-iPSC line derived from adult marmoset fibroblasts. The Cj-iPSCs showed potent pluripotency properties including development of mesodermal lineages in tumors after injection to immunocompromised mice, as well as ectoderm and endoderm lineages after in vitro differentiation regimens, demonstrating differentiated derivatives of all three embryonic layers...
June 21, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28634653/assessing-the-combined-toxicity-of-bmaa-and-its-isomers-2-4-dab-and-aeg-in-vitro-using-human-neuroblastoma-cells
#7
Brendan J Main, Kenneth J Rodgers
The non-protein amino acid (NPAA) ß-methylamino-L-alanine (BMAA) is produced by a diverse range of cyanobacteria, diatoms and dinoflagellates, and is present in both aquatic and terrestrial ecosystems globally. Exposure to BMAA has been implicated in the development of neurodegenerative diseases including amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD) and Parkinson's disease (PD). BMAA is often found in nature along with its structural isomers 2,4-diaminobutyric acid (2,4-DAB) and aminoethylglycine (AEG); however, the toxicity of these NPAAs in combination has not been examined...
June 20, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28634568/sirtuin-2-protects-neural-cells-from-oxidative-stress-and-is-elevated-in-neurodegeneration
#8
Preeti Singh, Peter S Hanson, Christopher M Morris
Sirtuins are highly conserved lysine deacetylases involved in ageing, energy production, and lifespan extension. The mammalian SIRT2 has been implicated in Parkinson's disease (PD) where studies suggest SIRT2 promotes neurodegeneration. We therefore evaluated the effects of SIRT2 manipulation in toxin treated SH-SY5Y cells and determined the expression and activity of SIRT2 in postmortem brain tissue from patients with PD. SH-SY5Y viability in response to oxidative stress induced by diquat or rotenone was measured following SIRT2 overexpression or inhibition of deacetylase activity, along with α-synuclein aggregation...
2017: Parkinson's Disease
https://www.readbyqxmd.com/read/28634551/mechanisms-and-consequences-of-dopamine-depletion-induced-attenuation-of-the-spinophilin-neurofilament-medium-interaction
#9
Andrew C Hiday, Michael C Edler, Asma B Salek, Cameron W Morris, Morrent Thang, Tyler J Rentz, Kristie L Rose, Lisa M Jones, Anthony J Baucum
Signaling changes that occur in the striatum following the loss of dopamine neurons in the Parkinson disease (PD) are poorly understood. While increases in the activity of kinases and decreases in the activity of phosphatases have been observed, the specific consequences of these changes are less well understood. Phosphatases, such as protein phosphatase 1 (PP1), are highly promiscuous and obtain substrate selectivity via targeting proteins. Spinophilin is the major PP1-targeting protein enriched in the postsynaptic density of striatal dendritic spines...
2017: Neural Plasticity
https://www.readbyqxmd.com/read/28634466/abnormal-temporal-coupling-of-tactile-perception-and-motor-action-in-parkinson-s-disease
#10
Antonella Conte, Daniele Belvisi, Matteo Tartaglia, Francesca Natalia Cortese, Viola Baione, Emanuele Battista, Xiao Y Zhu, Giovanni Fabbrini, Alfredo Berardelli
Evidence shows altered somatosensory temporal discrimination threshold (STDT) in Parkinson's disease in comparison to normal subjects. In healthy subjects, movement execution modulates STDT values through mechanisms of sensory gating. We investigated whether STDT modulation during movement execution in patients with Parkinson's disease differs from that in healthy subjects. In 24 patients with Parkinson's disease and 20 healthy subjects, we tested STDT at baseline and during index finger abductions (at movement onset "0", 100, and 200 ms thereafter)...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28634464/anti-inflammatory-and-neuroprotective-effects-of-co-ultrapealut-in-a-mouse-model-of-vascular-dementia
#11
Rosalba Siracusa, Daniela Impellizzeri, Marika Cordaro, Rosalia Crupi, Emanuela Esposito, Stefania Petrosino, Salvatore Cuzzocrea
Vascular dementia (VaD), the second most common cause of cognitive impairment in the population, is a disease that results from reduction in regional cerebral blood flow and involves oxidative stress and inflammation. Co-ultramicronized PEALut (co-ultra PEALut) is a new compound with beneficial effects, which include anti-inflammatory and antioxidant properties. Recently, co-ultraPEALut has been shown to exhibit neuroprotective effects in models of Parkinson's disease, cerebral ischemia and Alzheimer's disease...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28634349/synuclein-impairs-trafficking-and-signaling-of-bdnf-in-a-mouse-model-of-parkinson-s-disease
#12
Fang Fang, Wanlin Yang, Jazmin B Florio, Edward Rockenstein, Brian Spencer, Xavier M Orain, Stephanie X Dong, Huayan Li, Xuqiao Chen, Kijung Sung, Robert A Rissman, Eliezer Masliah, Jianqing Ding, Chengbiao Wu
Recent studies have demonstrated that hyperphosphorylation of tau protein plays a role in neuronal toxicities of α-synuclein (ASYN) in neurodegenerative disease such as familial Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and Parkinson's disease. Using a transgenic mouse model of Parkinson's disease (PD) that expresses GFP-ASYN driven by the PDGF-β promoter, we investigated how accumulation of ASYN impacted axonal function. We found that retrograde axonal trafficking of brain-derived neurotrophic factor (BDNF) in DIV7 cultures of E18 cortical neurons was markedly impaired at the embryonic stage, even though hyperphosphorylation of tau was not detectable in these neurons at this stage...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28634347/decreased-circulating-zinc-levels-in-parkinson-s-disease-a-meta-analysis-study
#13
Ke Du, Ming-Yan Liu, Xin Zhong, Min-Jie Wei
There is no consensus on the involvement of zinc (Zn) dysfunctions in Parkinson's Disease (PD). We performed a meta-analysis to evaluate whether circulating Zn levels in the serum, plasma, and cerebrospinal fluid (CSF) are altered in PD. Twenty-three published studies were selected by searching the databases of PubMed and China National Knowledge Infrastructure (CNKI). A total of 803 PD patients and 796 controls, 342 PD patients and 392 controls, and 135 PD patients and 93 controls were included to study Zn levels in the serum, plasma, and CSF, respectively...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28634343/falling-direction-can-predict-the-mechanism-of-recurrent-falls-in-advanced-parkinson-s-disease
#14
Jinyoung Youn, Yasuyuki Okuma, Minho Hwang, Dongyeop Kim, Jin Whan Cho
Falls are a common and disabling symptom in patients with Parkinson's disease (PD). For prevention, it is important to understand the pathophysiology of falls in PD patients, but the predictors for the possible mechanisms underlying such falls have not been clearly elucidated. In this prospective observational study, we investigated the implications of falling direction to predict the mechanisms of recurrent falls in PD patients. We enrolled 62 recurrent fallers with PD and divided them into two groups according to the main falling directions: 45 PD fallers who fell forward (forward fallers), and 17 PD fallers who fell in the other directions (non-forward fallers)...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28634107/chronic-pramipexole-treatment-induces-compulsive-behavior-in-rats-with-6-ohda-lesions-of-the-substantia-nigra-and-ventral-tegmental-area
#15
D Dardou, L Reyrolle, C Chassain, F Durif
Dopamine replacement therapy (DRT) reduces motor symptoms in Parkinson's disease (PD), but also induces impulsive-compulsive behavior (ICB) in up to 25% of PD patients. These non-motor side effects of DRT generally follow a gradual transition from impulsive to compulsive-like-i.e. repetitive, compelled, and non-pleasurable-behavior. Here, we investigated the effect of chronic pramipexole (PPX) treatment on the onset of compulsive-like behavior, measured via the post-training signal attenuation (PTSA) procedure, in rats with dopaminergic lesions...
June 17, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28633970/unified-neural-field-theory-of-brain-dynamics-underlying-oscillations-in-parkinson-s-disease-and-generalized-epilepsies
#16
E J Müller, S J van Albada, J W Kim, P A Robinson
The mechanisms underlying pathologically synchronized neural oscillations in Parkinson's disease (PD) and generalized epilepsies are explored in parallel via a physiologically-based neural field model of the corticothalamic-basal ganglia (CTBG) system. The basal ganglia (BG) are approximated as a single effective population and their roles in the modulation of oscillatory dynamics of the corticothalamic (CT) system and vice versa are analyzed. In addition to normal EEG rhythms, enhanced activity around 4 Hz and 20 Hz exists in the model, consistent with the characteristic frequencies observed in PD...
June 17, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28633628/olfactory-testing-in-consecutive-patients-referred-with-suspected-dementia
#17
Ib Thrane Christensen, Elna-Marie Larsson, Ida E Holm, Ole B F Nielsen, Stig Andersen
BACKGROUND: Alzheimer's disease (AD) is the most common cause of dementia and early and accurate diagnosis is important. Olfactory dysfunction is an early sign of AD. The contribution by test of olfactory function has been surveyed in AD vs a line of conditions but remains to be settled in the workup of unselected patients referred with suspected dementia. METHODS: We performed a two-step investigation: first, a comparative study of healthy controls and probable AD patients to test the applicability of the chosen scents (cuisine study); second, a study of consecutive patients referred to our geriatric outpatient clinic for suspected dementia with the investigating personnel blinded to the results of the Olfactory Test (blinded study)...
June 20, 2017: BMC Geriatrics
https://www.readbyqxmd.com/read/28633499/lateralized-basal-ganglia-vulnerability-to-pesticide-exposure-in-asymptomatic-agricultural-workers
#18
Mechelle M Lewis, Nicholas W Sterling, Guangwei Du, Eun-Young Lee, Grace Shyu, Michael Goldenberg, Thomas Allen, Christy Stetter, Lan Kong, Shedra Amy Snipes, Byron C Jones, Honglei Chen, Richard B Mailman, Xuemei Huang
Background: Pesticide exposure is linked to Parkinson's disease (PD), a neurodegenerative disorder marked by dopamine cell loss in the substantia nigra of the basal ganglia (BG) that often presents asymmetrically. We previously reported that pesticide-exposed agricultural workers (AW) have nigral diffusion tensor (DTI) changes. The current study sought to confirm this finding, and explore its hemisphere and regional specificity within BG structures using an independent sample population...
June 19, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28633346/tetramethylpyrazine-reverses-intracerebroventricular-streptozotocin-induced-memory-deficits-by-inhibiting-gsk-3%C3%AE
#19
Fen Lu, Xu Li, Wei Li, Ke Wei, Yong Yao, Qianlin Zhang, Xinliang Liang, Jiewen Zhang
Brain dysfunction, especially cognitive impairment, is one of the main complications in Alzheimer's disease (AD), which threatens the health of 46.8 million people worldwide. At present, the pathogenesis of cognitive dysfunction is only partially understood, and effective therapies for memory loss in AD remain elusive. Tetramethylpyrazine (TMP) is one of the major bioactive compounds purified from Chuanxiong, a Chinese herb used for the treatment of neurovascular and cardiovascular diseases. The neuroprotective properties of TMP are evident in some neurodegenerative diseases, including Parkinson's disease...
June 15, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/28632757/molecular-mechanism-of-drp1-assembly-studied-in-vitro-by-cryo-electron-microscopy
#20
Kaustuv Basu, Driss Lajoie, Tristan Aumentado-Armstrong, Jin Chen, Roman I Koning, Blaise Bossy, Mihnea Bostina, Attila Sik, Ella Bossy-Wetzel, Isabelle Rouiller
Mitochondria are dynamic organelles that continually adapt their morphology by fusion and fission events. An imbalance between fusion and fission has been linked to major neurodegenerative diseases, including Huntington's, Alzheimer's, and Parkinson's diseases. A member of the Dynamin superfamily, dynamin-related protein 1 (DRP1), a dynamin-related GTPase, is required for mitochondrial membrane fission. Self-assembly of DRP1 into oligomers in a GTP-dependent manner likely drives the division process. We show here that DRP1 self-assembles in two ways: i) in the presence of the non-hydrolysable GTP analog GMP-PNP into spiral-like structures of ~36 nm diameter; and ii) in the presence of GTP into rings composed of 13-18 monomers...
2017: PloS One
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