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https://www.readbyqxmd.com/read/27917933/inhibition-of-alpha-synuclein-aggregation-by-multifunctional-dopamine-agonists-assessed-by-a-novel-in-vitro-assay-and-an-in-vivo-drosophila-synucleinopathy-model
#1
Deepthi Yedlapudi, Gnanada S Joshi, Dan Luo, Sokol V Todi, Aloke K Dutta
Aggregation of alpha synuclein (α-syn) leading to dopaminergic neuronal death has been recognized as one of the main pathogenic factors in the initiation and progression of Parkinson's disease (PD). Consequently, α-syn has been targeted for the development of therapeutics for PD. We have developed a novel assay to screen compounds with α-syn modulating properties by mimicking recent findings from in vivo animal studies involving intrastriatal administration of pre-formed fibrils in mice, resulting in increased α-syn pathology accompanying the formation of Lewy-body (LB) type inclusions...
December 5, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27911312/increased-transforming-growth-factor-%C3%AE-2-in-the-neocortex-of-alzheimer-s-disease-and-dementia-with-lewy-bodies-is%C3%A2-correlated-with-disease-severity-and%C3%A2-soluble-a%C3%AE-42-load
#2
Joyce R Chong, Yuek Ling Chai, Jasinda H Lee, David Howlett, Johannes Attems, Clive G Ballard, Dag Aarsland, Paul T Francis, Christopher P Chen, Mitchell K P Lai
BACKGROUND: Of the three transforming growth factor (TGF)-β isoforms known, TGFβ1 deficits have been widely reported in Alzheimer's disease (AD) and studied as a potential therapeutic target. In contrast, the status of TGFβ2, which has been shown to mediate amyloid-β (Aβ)-mediated neuronal death, are unclear both in AD and in Lewy body dementias (LBD) with differential neuritic plaque and neurofibrillary tangle burden. OBJECTIVE: To measure neocortical TGFβ2 levels and their correlations with neuropathological and clinical markers of disease severity in a well-characterized cohort of AD as well as two clinical subtypes of LBD, dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), known to manifest relatively high and low Aβ plaque burden, respectively...
November 28, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27911311/risk-factors-and-pathological-substrates-associated-with-agitation-aggression-in-alzheimer-s-disease-a-preliminary-study-using-nacc-data
#3
Simrin Sennik, Tom A Schweizer, Corinne E Fischer, David G Munoz
BACKGROUND: Neuropsychiatric symptoms are common manifestations of Alzheimer's disease (AD). A number of studies have targeted psychosis, i.e., hallucinations and delusions in AD, but few have assessed agitation/aggression in AD. OBJECTIVE: To investigate the risk factors and pathological substrates associated with presence [A(+)] and absence [A(-)] of agitation/aggression (A) in autopsy-confirmed AD. METHODS: Data was collected from the UDS data as of 2015 on the NACC database...
November 28, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27911008/comparison-of-neuropathology-in-parkinson-s-disease-subjects-with-and-without-deep-brain-stimulation
#4
Gian D Pal, Bichun Ouyang, Geidy Serrano, Holly A Shill, Christopher Goetz, Glenn Stebbins, Leo Verhagen Metman, Erika Driver-Dunckley, Shyamal H Mehta, John N Caviness, Marwan N Sabbagh, Charles H Adler, Thomas G Beach
BACKGROUND: The aim of this postmortem study was to compare, in Parkinson's disease subjects with and without bilateral subthalamic nucleus deep brain stimulation (STN-DBS), the loss of pigmented neurons within the substantia nigra and pathological alpha-synuclein density within the SN and other brain regions. METHODS: PD subjects were identified from the Arizona Study of Aging and Neurodegenerative Disorders database (STN-DBS = 11, non-DBS = 156). Pigmented neuron loss scores within the substantia nigra as well as alpha-synuclein density scores within the substantia nigra and 9 other brain regions were compared, the latter individually and in summary as the Lewy body brain load score...
December 2, 2016: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/27911006/lrrk2-levels-and-phosphorylation-in-parkinson-s-disease-brain-and-cases-with-restricted-lewy-bodies
#5
Nicolas Dzamko, Amanda M Gysbers, Rina Bandopadhyay, Marc F Bolliger, Akiko Uchino, Ye Zhao, Masaki Takao, Sandrine Wauters, Wilma D J van de Berg, Junko Takahashi-Fujigasaki, R Jeremy Nichols, Janice L Holton, Shigeo Murayama, Glenda M Halliday
BACKGROUND: Leucine rich repeat kinase 2 (LRRK2) is a promising target for the treatment of Parkinson's disease; however, little is known about the expression of LRRK2 in human brain and if/how LRRK2 protein levels are altered in Parkinson's disease. OBJECTIVES: We measured the protein levels of LRRK2 as well as its phosphorylation on serines 910, 935, and 973 in the postmortem brain tissue of Parkinson's disease patients and aged controls with and without Lewy bodies...
December 2, 2016: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/27910919/group-benefit-associated-with-polymorphic-trichromacy-in-a-malagasy-primate-propithecus-verreauxi
#6
Carrie C Veilleux, Clara J Scarry, Anthony Di Fiore, E Christopher Kirk, Deborah A Bolnick, Rebecca J Lewis
In some primate lineages, polymorphisms in the X-linked M/LWS opsin gene have produced intraspecific variation in color vision. In these species, heterozygous females exhibit trichromacy, while males and homozygous females exhibit dichromacy. The evolutionary persistence of these polymorphisms suggests that balancing selection maintains color vision variation, possibly through a 'trichromat advantage' in detecting yellow/orange/red foods against foliage. We identified genetic evidence of polymorphic trichromacy in a population of Verreaux's sifaka (Propithecus verreauxi) at Kirindy Mitea National Park in Madagascar, and explored effects of color vision on reproductive success and feeding behavior using nine years of morphological, demographic, and feeding data...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27910826/enhancing-radiotherapy-for-lung-cancer-using-immunoadjuvants-delivered-in-situ-from-new-design-radiotherapy-biomaterials-a-preclinical-study
#7
Yao Hao, Sayeda Yasmin-Karim, Michele Moreau, Neeharika Sinha, Erno Sajo, Wilfred Ngwa
Studies show that radiotherapy of a primary tumor in combination with immunoadjuvants (IA) can result in increased survival or immune-mediated regression of metastasis outside the radiation field, a phenomenon known as abscopal effect. However, toxicities due to repeated systematic administration of IA have been shown to be a major obstacle in clinical trials. To minimize the toxicities and prime a more potent immune response, Ngwa et al have proposed that inert radiotherapy biomaterials such as fiducials could be upgraded to multifunctional ones loaded with IA for in situ delivery directly into the tumor sub-volume at no additional inconvenience to patients...
December 21, 2016: Physics in Medicine and Biology
https://www.readbyqxmd.com/read/27908269/levamisole-a-positive-allosteric-modulator-for-the-%C3%AE-3%C3%AE-4-nicotinic-acetylcholine-receptors-prevents-weight-gain-in-cd-1-mice-on-a-high-fat-diet
#8
Jeanne A Lewis, Jerrel L Yakel, Anshul A Pandya
Neuronal nicotinic acetylcholine receptors (nAChRs) regulate the function of multiple neurotransmitter pathways throughout the central nervous system. This includes nAChRs found on the proopiomelanocortin neurons in the hypothalamus. Activation of these nAChRs by nicotine causes a decrease in consumption of food in rodents. In this study, we tested the effect of subtype selective allosteric modulators for nAChRs on the body weight of CD-1 mice. Levamisole, an allosteric modulator for the α3β4 subtype of nAChRs, prevented weight gain in mice that were fed a high fat diet...
December 1, 2016: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/27905360/-orthostatic-hypotension-in-dementia-with-lewy-bodies
#9
A Sh Chimagomedova, O S Levin
The features of orthostatic hypotension in patients with dementia with Lewy bodies are considered. The early diagnosis of these disorders could prevent adverse conditions (falls and syncopes), improve activities of daily living and quality-of-life. Current approaches to treatment of orthostatic hypotension are analyzed.
2016: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
https://www.readbyqxmd.com/read/27905355/-cerebral-microbleeds-in-cerebrovascular-and-neurodegenerative-diseases-with-cognitive-impairment
#10
T A Polyakova, O S Levin
AIM: To study a role of cerebral microbleeds (CMB) in the diagnosis of main cerebrovascular and neurodegenerative diseases with cognitive impairment. MATERIAL AND METHODS: CMB were studied in 120 patients with Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and vascular dementia using 1.5T MRI in T2 * gradient echo. An impact of CMB on cognitive functions and the relationship with signs of vascular and neurodegenerative lesions of the brain were studied as well...
2016: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
https://www.readbyqxmd.com/read/27904705/paclitaxel-suppresses-collagen-induced-arthritis-a-reevaluation
#11
Yi Zhao, Zhi-Fang Chang, Ru Li, Zhan-Guo Li, Xiao-Xia Li, Lin Li
OBJECTIVE: To reevaluate the suppressive effect of paclitaxel (PTX) liposome on collagen-induced arthritis (CIA) in rats and explore its mechanisms. METHODS: Female Lewis rats were immunized with bovine type II collagen (CII) to induce arthritis. The rats with CIA were randomly divided into three groups: 5% GS control group, 2.5 mg/kg PTX treatment group and 1 mg/kg methotrexate (MTX) positive control group. The drugs were administered by intraperitoneal injection on the second day after arthritis onset...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27904575/alpha-synuclein-structure-functions-and-interactions
#12
REVIEW
Fatemeh Nouri Emamzadeh
At present, when a clinical diagnosis of Parkinson's disease (PD) is made, serious damage has already been done to nerve cells of the substantia nigra pars compacta. The diagnosis of PD in its earlier stages, before this irreversible damage, would be of enormous benefit for future treatment strategies designed to slow or halt the progression of this disease that possibly prevents accumulation of toxic aggregates. As a molecular biomarker for the detection of PD in its earlier stages, alpha-synuclein (α-syn), which is a key component of Lewy bodies, in which it is found in an aggregated and fibrillar form, has attracted considerable attention...
2016: Journal of Research in Medical Sciences: the Official Journal of Isfahan University of Medical Sciences
https://www.readbyqxmd.com/read/27901068/nanomechanical-properties-of-distinct-fibrillar-polymorphs-of-the-protein-%C3%AE-synuclein
#13
Ali Makky, Luc Bousset, Jérôme Polesel-Maris, Ronald Melki
Alpha-synuclein (α-Syn) is a small presynaptic protein of 140 amino acids. Its pathologic intracellular aggregation within the central nervous system yields protein fibrillar inclusions named Lewy bodies that are the hallmarks of Parkinson's disease (PD). In solution, pure α-Syn adopts an intrinsically disordered structure and assembles into fibrils that exhibit considerable morphological heterogeneity depending on their assembly conditions. We recently established tightly controlled experimental conditions allowing the assembly of α-Syn into highly homogeneous and pure polymorphs...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27900898/non-alzheimer-s-and-atypical-dementia-geschwind-michael-d-and-racine-caroline-eds-non-alzheimer-s-and-atypical-dementia-232pp-%C3%A2-94-99-wiley-blackwell-9781444336245-144433624x-formula-see-text
#14
(no author information available yet)
This comprehensive overview of atypical dementia, including Lewy body, prion diseases, and leukoencephalopathies, was written specifically for multidisciplinary teams.
November 30, 2016: Nursing Older People
https://www.readbyqxmd.com/read/27899389/high-dose-rivastigmine-in-the-symptom-management-of-lewy-body-dementia
#15
Joseph Marwan Nour, Leonidas Chouliaras, Lilian Hickey
A man presented in late 2004 at the age of 65 with a decline in memory. He was diagnosed with Lewy body dementia and started on 3 mg rivastigmine a day, which made a marked clinical improvement. He lived with the illness for 10 years, over which time the dose of acetylcholinesterase inhibitors (ChEI) he took rose to two 9.5 mg rivastigmine patches and 7.5 mg donepezil, significantly above British National Formulary (BNF) limits. He demonstrated clear clinical response to ChEI and showed improvements in alertness and functioning...
November 29, 2016: BMJ Case Reports
https://www.readbyqxmd.com/read/27899296/targeting-the-norepinephrinergic-system-in-parkinson-s-disease-and-related-disorders-the-locus-coeruleus-story
#16
Yannick Vermeiren, Peter P De Deyn
Parkinson's disease (PD), dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) are related, progressive and debilitating neurodegenerative disorders with hallmark features that include a variety of motor and non-motor symptoms (behavioral, autonomic and cognitive dysfunction). For almost half a century, the motor aspects have been attributed to Lewy pathology (LP) predominantly in the substantia nigra (SN), causing a major loss of dopaminergic neurons. However, the relative success of dopaminergic replacement therapies for alleviation of solely the parkinsonian features has prompted researchers to further explore other monoaminergic strategies which may tackle all PD-related aspects...
November 26, 2016: Neurochemistry International
https://www.readbyqxmd.com/read/27897064/diagnosis-of-dementia-with-lewy-bodies-can-123-i-imp-and-123-i-mibg-scintigraphy-yield-new-core-features
#17
Fumi Sakamoto, Shinya Shiraishi, Noriko Tsuda, Mamoru Hashimoto, Seiji Tomiguchi, Manabu Ikeda, Yasuyuki Yamashita
OBJECTIVE: Since the clinical symptoms of different types of dementia frequently overlap, especially in the earlier stages at onset, it is difficult to distinguish dementias with Lewy bodies (DLB) from other neurodegenerative dementias based on their clinical manifestations alone. Nuclear medicine imaging has been reported as a high-value index for the objective evaluation and diagnosis of DLB. The aim of this study was to evaluate whether nuclear medicine imaging findings may yield core features to be added to the diagnosis of DLB...
November 29, 2016: British Journal of Radiology
https://www.readbyqxmd.com/read/27892477/nanomolar-oligomerization-and-selective-co-aggregation-of-%C3%AE-synuclein-pathogenic-mutants-revealed-by-single-molecule-fluorescence
#18
Emma Sierecki, Nichole Giles, Quill Bowden, Mark E Polinkovsky, Janina Steinbeck, Nicholas Arrioti, Diya Rahman, Akshay Bhumkar, Philip R Nicovich, Ian Ross, Robert G Parton, Till Böcking, Yann Gambin
Protein aggregation is a hallmark of many neurodegenerative diseases, notably Alzheimer's and Parkinson's disease. Parkinson's disease is characterized by the presence of Lewy bodies, abnormal aggregates mainly composed of α-synuclein. Moreover, cases of familial Parkinson's disease have been linked to mutations in α-synuclein. In this study, we compared the behavior of wild-type (WT) α-synuclein and five of its pathological mutants (A30P, E46K, H50Q, G51D and A53T). To this end, single-molecule fluorescence detection was coupled to cell-free protein expression to measure precisely the oligomerization of proteins without purification, denaturation or labelling steps...
November 28, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27891726/everyday-conversation-in-dementia-a-review-of-the-literature-to-inform-research-and-practice
#19
REVIEW
Jacqueline Kindell, John Keady, Karen Sage, Ray Wilkinson
BACKGROUND: There has been increasing interest in dementia care in recent years, including how practitioners, service providers and society in general can help individuals to live well with the condition. An important aspect to this is provision of advice to ensure conversation partners effectively support the person with dementia in conversation. AIMS: To provide a descriptive review of the literature examining everyday conversation in dementia in order to inform practice and research...
November 27, 2016: International Journal of Language & Communication Disorders
https://www.readbyqxmd.com/read/27890431/neuroprotective-mechanisms-of-plant-extracts-against-mptp-induced-neurotoxicity-future-applications-in-parkinson-s-disease
#20
REVIEW
Abdelrahman Ibrahim Abushouk, Ahmed Negida, Hussien Ahmed, Mohamed M Abdel-Daim
Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease, affecting about seven to 10 million patients worldwide. The major pathological features of PD are loss of dopaminergic neurons in the nigrostriatal pathway and accumulation of alpha-synuclein molecules, forming Lewy bodies. Until now, there is no effective cure for PD, and investigators are searching for neuroprotective strategies to stop or slow the disease progression. The MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) induced neurotoxicity of the nigrostriatal pathway has been used to initiate PD in animal models...
November 24, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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