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Vanesa Nozal, Ana Martinez
Tau-tubuline kinases (TTBK) are a family of serine/threonine and tyrosine kinases recently discovered and implicated in the phosphorylation of important substrates such as tau, tubuline or TDP-43. Its two homologs, TTBK1 and TTBK2, show different expression patterns and different involvements in physiological mechanisms of great importance such as mitosis, ciliogenesis and neurotransmission. Their phosphorylation activity has also linked them to the development of neurodegenerative diseases like Alzheimer's disease, amyotrophic lateral sclerosis or spinocerebellar ataxia type 11...
October 15, 2018: European Journal of Medicinal Chemistry
Alessandro Palmioli, Sara Bertuzzi, Ada De Luigi, Laura Colombo, Barbara La Ferla, Mario Salmona, Ivano De Noni, Cristina Airoldi
The growing interest in medicinal plants for the identification of new bioactive compounds and the formulation of new nutraceuticals and drugs prompted us to develop a powerful experimental approach allowing the detailed metabolic profiling of complex plant extracts, the identification of ligands of macromolecular targets of biomedical relevance and a preliminary characterization of their biological activity. To this end, we selected Peucedanum ostruthium, a plant traditionally employed in Austria and Italy for its several potential therapeutic applications, as case study...
October 12, 2018: Bioorganic Chemistry
Jie Zhao, Wanxia Gao, Zhen Yang, Hailing Li, Zhonghong Gao
It is known that copper ion (Cu(II)) binds to amyloid-β peptide (Aβ), induces Aβ oligomer formation and ultimately exacerbates Aβ-aggregation neurotoxicity in Alzheimer's disease (AD). It becomes interesting to know that how this chemical modification of Aβ would affect interaction of Aβ and Cu(II) and their roles in the development of AD. In this work, we investigated the interaction of Aβ1-42 nitration with the toxic Cu(II). It showed that Cu(II)induced Aβ1-42 nitration in the presence of nitrite and hydrogen peroxide...
October 16, 2018: Journal of Inorganic Biochemistry
Emma Delhaye, Mohamed Ali Bahri, Eric Salmon, Christine Bastin
Unitization, the capacity to encode associations as one integrated entity, can enhance associative memory in populations with an associative memory deficit by promoting familiarity-based associative recognition. Patients with Alzheimer's disease (AD) are typically impaired in associative memory compared with healthy controls but do not benefit from unitization strategies. Using fragmented pictures of objects, this study aimed at assessing which of the cognitive processes that compose unitization is actually affected in AD: the retrieval of unitized representations itself, or some earlier stages of processing, such as the integration process at a perceptual or conceptual stage of representation...
September 22, 2018: Neurobiology of Aging
Mercedes Lachén-Montes, Andrea González-Morales, Ibon Iloro, Felix Elortza, Isidre Ferrer, Djordje Gveric, Joaquín Fernández-Irigoyen, Enrique Santamaría
Olfactory dysfunction is one of the earliest features in Lewy-type alpha-synucleinopathies (LTSs) such as Parkinson's disease (PD). However, the underlying molecular mechanisms associated to smell impairment are poorly understood. Applying mass spectrometry-based quantitative proteomics in postmortem olfactory bulbs across limbic, early-neocortical, and neocortical LTS stages of parkinsonian patients, a proteostasis impairment, was observed, identifying 268 differentially expressed proteins between controls and PD phenotypes...
September 25, 2018: Neurobiology of Aging
Nahid Zokaei, Giedrė Čepukaitytė, Alexander G Board, Clare E Mackay, Masud Husain, Anna Christina Nobre
Short- and long-term memory performance as a function of apolipoprotein-E (APOE) genotype was examined in older, healthy individuals using sensitive and comparable tasks to provide a more detailed description of influences of the ε4 allele (highest genetic risk factor for Alzheimer's disease) on memory. Older heterozygous and homozygous ε4 carriers and noncarriers performed 2 tasks of memory. Both tasks allowed us to measure memory for item identity and locations, using a sensitive, continuous measure of report...
September 25, 2018: Neurobiology of Aging
Candas Pinar, Rene Almeling, Shana Kushner Gadarian
Prospective parents have long been able to learn details about their offspring's DNA, and social scientists have demonstrated that this form of genetic information influences reproductive decision-making. Now, new tests offer adults information about their own genetic risk for common diseases that begin later in life, raising new questions about whether this kind of personal risk will also affect fertility plans. Drawing on a survey experiment (N = 223) that assigned individuals a genetic risk (20%, 30% … 80%) for an adult-onset disease (heart disease, colon cancer, Alzheimer's Disease), this study examines whether such risks lead people to reconsider their plans to have children...
September 27, 2018: Social Science & Medicine
Chen Zhao, Chunchen Zhang, Zheng Xing, Zeeshan Ahmad, Jing-Song Li, Ming-Wei Chang
Ganoderma, has been used for clinical applications for thousands of years as a highly-nutritious and significantly-effective medicinal herb. The active components and efficacy of Ganoderma are constantly being explored and supplemented every year. In recent years, more and more literature has reported the pharmacological effects of Ganoderma on anti-tumor, liver protection and immunity enhancement, especially on neuroprotection. Numerous research works on the neuroprotective effects of Ganoderma have been documented (e...
October 17, 2018: International Journal of Biological Macromolecules
Mulin Xu, Yu Liu, Yi Huang, Jinli Wang, Jinhua Yan, Le Zhang, Cuntai Zhang
Frontal cortical dysfunction is a fundamental pathology contributing to age-associated behavioral and cognitive deficits that predispose older adults to neurodegenerative diseases. It is established that aging increases the risk of frontal cortical dysfunction; however, the underlying molecular mechanism remains elusive. Here, we used an integrative meta-analysis to combine five frontal cortex microarray studies with a combined sample population of 161 younger and 155 older individuals. A network-based analysis was used to describe an outline of human frontal cortical aging to identify core genes whose expression changes with age and to reveal the interrelationships among these genes...
October 20, 2018: Aging
Aurelie Leplus, Inger Lauritzen, Christophe Melon, Lydia Kerkerian-Le Goff, Denys Fontaine, Frederic Checler
Recent studies have suggested deep brain stimulation (DBS) as a promising therapy in patients with Alzheimer's disease (AD). Particularly, the stimulation of the forniceal area was found to slow down the cognitive decline of some AD patients, but the biochemical and anatomical modifications underlying these effects remain poorly understood. We evaluated the effects of chronic forniceal stimulation on amyloid burden, inflammation, and neuronal loss in a transgenic Alzheimer rat model TgF344-AD, as well as in age-matched control rats...
October 19, 2018: Brain Structure & Function
Moussa B H Youdim
In early 1920s, tyramine oxidase was discovered that metabolized tyramine and in 1933 Blaschko demonstrated that this enzyme also metabolized adrenaline, noradrenaline and dopamine. Zeller gave it the name monoamine oxidase (MAO) to distinguish it from the enzyme that oxidatively deaminated diamines. MAO was recognized as an enzyme of crucial interest to pharmacologists because it catalyzed the major inactivation pathway for the catecholamines (and, later, 5-hydroxytryptamine, as well). Within the few decade, the inhibitors of MAO were discovered and introduced for the treatment of depressive illness which was established clinically...
October 19, 2018: Journal of Neural Transmission
Hirota Fujiki, Eisaburo Sueoka, Tatsuro Watanabe, Masami Suganuma
PURPOSE: The okadaic acid class of tumor promoters, which are inhibitors of protein phosphatases 1 and 2A (PP1 and PP2A), induced tumor promotion in mouse skin, rat glandular stomach, and rat liver. Endogenous protein inhibitors of PP2A, SET and CIP2A, were up-regulated in various human cancers, so it is vital to review the essential mechanisms of tumor promotion by the okadaic acid class compounds, together with cancer progression by SET and CIP2A in humans. RESULTS AND DISCUSSION: The first part of this review introduces the okadaic acid class compounds and the mechanism of tumor promotion: (1) inhibition of PP1 and PP2A activities of the okadaic acid class compounds; (2) some topics of tumor promotion; (3) TNF-α gene expression as a central mediator in tumor promotion; (4) exposure to the okadaic acid class of tumor promoters in relation to human cancer...
October 20, 2018: Journal of Cancer Research and Clinical Oncology
Tuane Cristine R G Vieira, Jerson L Silva
Prion (PrPC ) is an endogenous protein found mainly in the nervous system, and its misfolded isoform (PrPSc ) is associated with a group of neurodegenerative disorders known as transmissible spongiform encephalopathies, or simply prion diseases. The PrPSc isoform shows an intriguing ability to self-perpetuate, acting as template for PrPC misfolding and consequent aggregation. Aggregation in vitro and in vivo follows a fibrillation processes that is associated with neurodegeneration. Therefore, it is important to investigate and understand the molecular mechanisms involved in this process; such understanding also allows investigation of the action of possible candidate molecules to inhibit this process...
2019: Methods in Molecular Biology
Linda Koch
No abstract text is available yet for this article.
October 19, 2018: Nature Reviews. Genetics
Kathrin M Kniewallner, Bettina M Foidl, Christian Humpel
Platelets are anuclear blood cells and play a major role in hemostasis and thrombosis. Platelets express amyloid-precursor protein (APP), release beta-amyloid (Aβ) and are stimulated (pre-activated) in Alzheimer's disease (AD). We hypothesize that such stimulated platelets severely damage brain vessels which subsequently leads to cerebrovascular damage in AD. In order to study this issue we isolated platelets from AD mice (expressing APP with the Swedish-Dutch-Iowa mutations), labeled them with the red fluorescent dye PKH26 and transcardially infused these freshly isolated platelets into the brains of anesthetized healthy C57BL6 wildtype mice...
October 19, 2018: Scientific Reports
Xiang Zhu, Matthew Stephens
Genome-wide association studies (GWAS) aim to identify genetic factors associated with phenotypes. Standard analyses test variants for associations individually. However, variant-level associations are hard to identify and can be difficult to interpret biologically. Enrichment analyses help address both problems by targeting sets of biologically related variants. Here we introduce a new model-based enrichment method that requires only GWAS summary statistics. Applying this method to interrogate 4,026 gene sets in 31 human phenotypes identifies many previously-unreported enrichments, including enrichments of endochondral ossification pathway for height, NFAT-dependent transcription pathway for rheumatoid arthritis, brain-related genes for coronary artery disease, and liver-related genes for Alzheimer's disease...
October 19, 2018: Nature Communications
Travis Rush, Jose Martinez-Hernandez, Marc Dollmeyer, Marie Lise Frandemiche, Eve Borel, Sylvie Boisseau, Muriel Jacquier-Sarlin, Alain Buisson
Amyloid-β (Aβ) drives the synaptic impairment and dendritic spine loss characteristic of Alzheimer's disease (AD), but how Aβ affects the actin cytoskeleton remains unknown and contentious. The actin-binding protein, cofilin-1 (cof1), is a major regulator of actin dynamics in dendritic spines, and is subject to phospho-regulation by multiple pathways, including the Rho-associated protein kinase (ROCK) pathway. While cof1 is implicated as a driver of the synaptotoxicity characteristic of the early phases of AD pathophysiology, questions remain about the molecular mechanisms involved...
October 19, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Colin Groot, Carole H Sudre, Frederik Barkhof, Charlotte E Teunissen, Bart N M van Berckel, Sang Won Seo, Sébastien Ourselin, Philip Scheltens, M Jorge Cardoso, Wiesje M van der Flier, Rik Ossenkoppele
OBJECTIVE: To examine the clinical phenotype, gray matter atrophy patterns, and small vessel disease in patients who developed prodromal or probable Alzheimer disease dementia, despite carrying the protective APOE ε2 allele. METHODS: We included 36 β-amyloid-positive (by CSF or PET) APOE ε2 carriers (all ε2/ε3) with mild cognitive impairment or dementia due to Alzheimer disease who were matched for age and diagnosis (ratio 1:2) to APOE ε3 homozygotes and APOE ε4 carriers (70% ε3/ε4 and 30% ε4/ε4)...
October 19, 2018: Neurology
Christian B Lessard, Samuel L Malnik, Yingyue Zhou, Thomas B Ladd, Pedro E Cruz, Yong Ran, Thomas E Mahan, Paramita Chakrabaty, David M Holtzman, Jason D Ulrich, Marco Colonna, Todd E Golde
Rare coding variants in the triggering receptor expressed on myeloid cells 2 (TREM2) are associated with increased risk for Alzheimer's disease (AD), but how they confer this risk remains uncertain. We assessed binding of TREM2, AD-associated TREM2 variants to various forms of Aβ and APOE in multiple assays. TREM2 interacts directly with various forms of Aβ, with highest affinity interactions observed between TREM2 and soluble Aβ42 oligomers. High-affinity binding of TREM2 to Aβ oligomers is characterized by very slow dissociation...
October 19, 2018: EMBO Molecular Medicine
Liselotte De Wit, Deirdre O'Shea, Melanie Chandler, Tripti Bhaskar, Jared Tanner, Prashanthi Vemuri, Julia Crook, Miranda Morris, Glenn Smith
BACKGROUND: Amnestic mild cognitive impairment (aMCI) is considered a risk state for the development of dementia due to Alzheimer's disease. It is also a period in which interventions may be most effective in slowing progression to dementia. Computerized cognitive training and increased physical activity have shown to be among the most promising interventions. However, current evidence from randomized controlled trials comparing cognitive training, physical activity, and an active control is inconsistent...
October 19, 2018: Trials
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