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https://www.readbyqxmd.com/read/29458203/precision-pharmacology-for-alzheimer-s-disease
#1
REVIEW
Harald Hampel, Andrea Vergallo, Lisi Flores Aguilar, Norbert Benda, Karl Broich, A Claudio Cuello, Jeffrey Cummings, Bruno Dubois, Howard J Federoff, Massimo Fiandaca, Remy Genthon, Marion Haberkamp, Eric Karran, Mark Mapstone, George Perry, Lon S Schneider, Lindsay A Welikovitch, Janet Woodcock, Filippo Baldacci, Simone Lista
The complex multifactorial nature of polygenic Alzheimer's disease (AD) presents significant challenges for drug development. AD pathophysiology is progressing in a non-linear dynamic fashion across multiple systems levels - from molecules to organ systems - and through adaptation, to compensation, and decompensation to systems failure. Adaptation and compensation maintain homeostasis: a dynamic equilibrium resulting from the dynamic non-linear interaction between genome, epigenome, and environment. An individual vulnerability to stressors exists on the basis of individual triggers, drivers, and thresholds accounting for the initiation and failure of adaptive and compensatory responses...
February 16, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29457783/cellular-senescence-in-brain-aging-and-neurodegenerative-diseases-evidence-and-perspectives
#2
Darren J Baker, Ronald C Petersen
Along with a general decline in overall health, most chronic degenerative human diseases are inherently associated with increasing age. Age-associated cognitive impairments and neurodegenerative diseases, such as Parkinson's and Alzheimer's diseases, are potentially debilitating conditions that lack viable options for treatment, resulting in a tremendous economic and societal cost. Most high-profile clinical trials for neurodegenerative diseases have led to inefficacious results, suggesting that novel approaches to treating these pathologies are needed...
February 19, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29457487/dementia-management-strategies-associated-with-neuropsychiatric-symptoms-of-elderly-people-with-alzheimer-s-disease
#3
Lais Lopes Delfino, Ricardo Shoiti Komatsu, Caroline Komatsu, Anita Liberalesso Neri, Meire Cachioni
This study aims to investigate the association between management and communication strategies and the presence of neuropsychiatric symptoms presented by elderly people with Alzheimer's disease. One hundred and thirty-four family caregivers answered a questionnaire with socio-demographic data and questions regarding the care context, the Small Communication Strategies Scale, the Dementia Management Strategy Scale, and the Neuropsychiatric Inventory. Caregivers used the criticism management strategy more when the elderly presented hallucination, agitation, depression, anxiety, irritability, nighttime behavior, and appetite abnormalities...
January 1, 2018: Dementia
https://www.readbyqxmd.com/read/29456801/identification-of-potent-indoleamine-2-3-dioxygenase-1-ido1-inhibitors-based-on-a-phenylimidazole-scaffold
#4
Michael G Brant, Jake Goodwin-Tindall, Kurt R Stover, Paul M Stafford, Fan Wu, Autumn R Meek, Paolo Schiavini, Stephanie Wohnig, Donald F Weaver
Inhibition of indoleamine 2,3-dioxygenase (IDO1) is an attractive immunotherapeutic approach for the treatment of a variety of cancers. Dysregulation of this enzyme has also been implicated in other disorders including Alzheimer's disease and arthritis. Herein, we report the structure-based design of two related series of molecules: N 1-substituted 5-indoleimidazoles and N 1-substituted 5-phenylimidazoles. The latter (and more potent) series was accessed through an unexpected rearrangement of an imine intermediate during a Van Leusen imidazole synthesis reaction...
February 8, 2018: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29456504/a-review-on-central-nervous-system-effects-of-gastrodin
#5
REVIEW
Yuan Liu, Jialiang Gao, Min Peng, Hongyan Meng, Hongbo Ma, Pingping Cai, Yuan Xu, Qiong Zhao, Guomin Si
Rhizoma Gastrodiae (also known as Tian ma ), the dried rhizome of Gastrodia elata Blume, is a famous Chinese herb that has been traditionally used for the treatment of headache, dizziness, spasm, epilepsy, stoke, amnesia and other disorders for centuries. Gastrodin, a phenolic glycoside, is the main bioactive constituent of Rhizoma Gastrodiae . Since identified in 1978, gastrodin has been extensively investigated on its pharmacological properties. In this article, we reviewed the central nervous system (CNS) effects of gastrodin in preclinical models of CNS disorders including epilepsy, Alzheimer's disease, Parkinson's disease, affective disorders, cerebral ischemia/reperfusion, cognitive impairment as well as the underlying mechanisms involved and, where possible, clinical data that support the pharmacological activities...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29456501/recommendations-for-the-design-of-serious-games-in-neurodegenerative-diseases
#6
Grégory Ben-Sadoun, Valeria Manera, Julian Alvarez, Guillaume Sacco, Philippe Robert
The use of Serious Games (SG) in the health domain is expanding. In the field of Neurodegenerative Diseases (ND) such as Alzheimer's Disease, SG are currently employed to provide alternative solutions for patients' treatment, stimulation, and rehabilitation. The design of SG for people with ND implies collaborations between professionals in ND and professionals in SG design. As the field is quite young, professionals specialized in both ND and SG are still rare, and recommendations for the design of SG for people with ND are still missing...
2018: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29454607/italian-wikipedia-and-epilepsy-an-infodemiological-study-of-online-information-seeking-behavior
#7
Francesco Brigo, Simona Lattanzi, Giorgia Giussani, Laura Tassi, Nicola Pietrafusa, Carlo Andrea Galimberti, Raffaele Nardone, Nicola Luigi Bragazzi, Oriano Mecarelli
Wikipedia is the most commonly accessed source of health information by both healthcare professionals and the lay public worldwide. We aimed to evaluate information-seeking behavior of Internet users searching the Italian Wikipedia for articles related to epilepsy and its treatment. Using Pageviews Analysis, we assessed the total and mean monthly views of articles from the Italian Wikipedia devoted to epilepsy, epileptic syndromes, seizure type, and antiepileptic drugs (AEDs) from January 1, 2015 to October 31, 2017...
February 14, 2018: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/29454581/emerging-roles-of-microglial-cathepsins-in-neurodegenerative-disease
#8
REVIEW
Jessica R Lowry, Andis Klegeris
Alzheimer's disease (AD) is one of the leading causes of dementia, and its prevalence is expected to increase dramatically due to the aging global population. Microglia-driven neuroinflammation may contribute to the progression of AD. Microglia, the immune cells of the central nervous system (CNS), become chronically activated by the pathological proteins of AD including amyloid-β peptides (Aβ). Such adversely activated microglia secrete mediators that promote inflammation and damage neurons. Cathepsins are proteases that are expressed by all brain cell types, and most of them are found both intra- and extra-cellularly...
February 15, 2018: Brain Research Bulletin
https://www.readbyqxmd.com/read/29454006/predicting-cognitive-decline-with-deep-learning-of-brain-metabolism-and-amyloid-imaging
#9
Hongyoon Choi, Kyong Hwan Jin
For effective treatment of Alzheimer's disease (AD), it is important to identify subjects who are most likely to exhibit rapid cognitive decline. We aimed to develop an automatic image interpretation system based on a deep convolutional neural network (CNN) which can accurately predict future cognitive decline in mild cognitive impairment (MCI) patients using flurodeoxyglucose and florbetapir positron emission tomography (PET). PET images of 139 patients with AD, 171 patients with MCI and 182 normal subjects obtained from Alzheimer's Disease Neuroimaging Initiative database were used...
February 14, 2018: Behavioural Brain Research
https://www.readbyqxmd.com/read/29453958/age-dependent-effects-of-dimethyl-fumarate-on-cognitive-and-neuropathological-features-in-the-streptozotocin-induced-rat-model-of-alzheimer-s-disease
#10
Irena Majkutewicz, Ewelina Kurowska, Magdalena Podlacha, Dorota Myślińska, Beata Grembecka, Jan Ruciński, Karolina Pierzynowska, Danuta Wrona
We previously demonstrated that dimethyl fumarate (DMF), an anti-oxidative and immunosuppresive compound, prevents intracerebroventricular (ICV) streptozotocin-induced disruption of spatial memory and neurodegeneration in 4-month-old rats. The present study evaluated the influence of age on DMF's therapeutic effect. Aged rats (22-months-old, n=40) were provided rodent chow containing DMF (0.4%) and given ICV injections of streptozotocin (STZ) or vehicle (Sham) on days 2 and 4. Spatial memory was evaluated using the Morris water maze (MWM) on days 14-21...
February 14, 2018: Brain Research
https://www.readbyqxmd.com/read/29453901/shedding-light-on-aberrant-interactions-a-review-of-modern-tools-for-studying-protein-aggregates
#11
REVIEW
Franziska Kundel, Laura Tosatto, Daniel R Whiten, David C Wirthensohn, Mathew H Horrocks, David Klenerman
The link between protein aggregation and neurodegenerative disease is well established. However, given the heterogeneity of species formed during the aggregation process, it is difficult to delineate details of the molecular events involved in generating pathological aggregates from those producing soluble monomers. As aberrant aggregates are possible pharmacological targets for the treatment of neurodegenerative diseases, the need to observe and characterise soluble oligomers has pushed traditional biophysical techniques to their limits, leading to the development of a plethora of new tools capable of detecting soluble oligomers with high precision and specificity...
February 17, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29453339/a-role-for-tau-in-learning-memory-and-synaptic-plasticity
#12
Fabrizio Biundo, Dolores Del Prete, Hong Zhang, Ottavio Arancio, Luciano D'Adamio
Tau plays a pivotal role in the pathogenesis of neurodegenerative disorders: mutations in the gene encoding for tau (MAPT) are linked to Fronto-temporal Dementia (FTD) and hyper-phosphorylated aggregates of tau forming neurofibrillary tangles (NFTs) that constitute a pathological hallmark of Alzheimer disease (AD) and FTD. Accordingly, tau is a favored therapeutic target for the treatment of these diseases. Given the criticality of tau to dementia's pathogenesis and therapy, it is important to understand the physiological function of tau in the central nervous system...
February 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29453052/ac-lvffark-nh-2-conjugation-to-%C3%AE-cyclodextrin-exhibits-significantly-enhanced-performance-on-inhibiting-amyloid-%C3%AE-protein-fibrillogenesis-and-cytotoxicity
#13
Huan Zhang, Xiaoyan Dong, Fufeng Liu, Jie Zheng, Yan Sun
Inhibition of amyloid β-protein (Aβ) aggregation is of significance for the potential treatment of Alzheimer's disease. We have herein conjugated heptapeptide Ac-LVFFARK-NH 2 (LK7) to β-cyclodextrin (βCyD) and studied the inhibitory effect of the LK7-βCyD conjugate on Aβ aggregation. The conjugation significantly improved the peptide solubility and suppressed the self-assembly propensity. This led to 30% increase of the binding affinity of LK7 for Aβ in the conjugate due to increased hydrophobic interactions...
February 11, 2018: Biophysical Chemistry
https://www.readbyqxmd.com/read/29452686/technological-advances-and-changing-indications-for-lumbar-puncture-in-neurological-disorders
#14
REVIEW
Joost M Costerus, Matthijs C Brouwer, Diederik van de Beek
Technological advances have changed the indications for and the way in which lumbar puncture is done. Suspected CNS infection remains the most common indication for lumbar puncture, but new molecular techniques have broadened CSF analysis indications, such as the determination of neuronal autoantibodies in autoimmune encephalitis. New screening techniques have increased sensitvity for pathogen detection and can be used to identify pathogens that were previously unknown to cause CNS infections. Evidence suggests that potential treatments for neurodegenerative diseases, such as Alzheimer's disease, will rely on early detection of the disease with the use of CSF biomarkers...
March 2018: Lancet Neurology
https://www.readbyqxmd.com/read/29452684/evaluation-of-the-safety-tolerability-and-efficacy-of-pimavanserin-versus-placebo-in-patients-with-alzheimer-s-disease-psychosis-a-phase-2-randomised-placebo-controlled-double-blind-study
#15
Clive Ballard, Carol Banister, Zunera Khan, Jeffrey Cummings, George Demos, Bruce Coate, James M Youakim, Randall Owen, Srdjan Stankovic
BACKGROUND: Pimavanserin is a selective 5-HT 2A receptor inverse agonist and antagonist approved in the USA for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis. No safe or effective pharmacological treatment is approved for psychosis in patients with Alzheimer's disease. Therefore, we aimed to evaluate the safety, tolerability, and efficacy of pimavanserin versus placebo in patients with Alzheimer's disease psychosis. METHODS: We did a phase 2, randomised, double-blind, placebo-controlled, single-centre (with multiple affiliated nursing home sites across the UK) study...
March 2018: Lancet Neurology
https://www.readbyqxmd.com/read/29451200/modulation-of-mitochondrial-bioenergetics-as-a-therapeutic-strategy-in-alzheimer-s-disease
#16
REVIEW
Isaac G Onyango
Alzheimer's disease (AD) is an increasingly pressing worldwide public-health, social, political and economic concern. Despite significant investment in multiple traditional therapeutic strategies that have achieved success in preclinical models addressing the pathological hallmarks of the disease, these efforts have not translated into any effective disease-modifying therapies. This could be because interventions are being tested too late in the disease process. While existing therapies provide symptomatic and clinical benefit, they do not fully address the molecular abnormalities that occur in AD neurons...
January 2018: Neural Regeneration Research
https://www.readbyqxmd.com/read/29449801/lithium-inhibits-gsk3%C3%AE-and-augments-glun2a-receptor-expression-in-the-prefrontal-cortex
#17
Sarah A Monaco, Brielle R Ferguson, Wen-Jun Gao
Glycogen synthase kinase 3β (GSK3β) is a highly conserved serine/threonine kinase that has been implicated in both psychiatric and neurodegenerative diseases including schizophrenia, bipolar disorder, and Alzheimer's disease; therefore regulating its activity has become an important strategy for treatment of cognitive impairments in these disorders. This study examines the effects of lithium on GSK3β and its interaction with β-catenin and NMDA receptors within the prefrontal cortex. Lithium, a clinically relevant drug commonly prescribed as a mood stabilizer for psychiatric disorders, significantly increased levels of phosphorylated GSK3β serine 9, an inhibitory phosphorylation site, and decreased β-catenin ser33/37/thr41 phosphorylation in vitro , indicating GSK3β inhibition and reduced β-catenin degradation...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29449587/the-mechanisms-of-bushen-yizhi-formula-as-a-therapeutic-agent-against-alzheimer-s-disease
#18
Haobin Cai, Yunxia Luo, Xin Yan, Peng Ding, Yujie Huang, Shuhuan Fang, Rong Zhang, Yunbo Chen, Zhouke Guo, Jiansong Fang, Qi Wang, Jun Xu
Bushen-Yizhi prescription (BSYZ) has been an effective traditional Chinese medicine (TCM) prescription in treating Alzheimer's disease (AD) for hundreds of years. However, the underlying mechanisms have not been fully elucidated yet. In this work, a systems pharmacology approach was developed to reveal the underlying molecular mechanisms of BSYZ in treating AD. First, we obtained 329 candidate compounds of BSYZ by in silico ADME/T filter analysis and 138 AD-related targets were predicted by our in-house WEGA algorithm via mapping predicted targets into AD-related proteins...
February 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29448961/nuclear-receptor-agonist-driven-modification-of-inflammation-and-amyloid-pathology-enhances-and-sustains-cognitive-improvements-in-a-mouse-model-of-alzheimer-s-disease
#19
Brad T Casali, Erin G Reed-Geaghan, Gary E Landreth
BACKGROUND: Alzheimer's disease (AD) is a highly prevalent neurodegenerative disorder characterized by pathological hallmarks of beta-amyloid plaque deposits, tau pathology, inflammation, and cognitive decline. Treatment remains a clinical obstacle due to lack of effective therapeutics. Agonists targeting nuclear receptors, such as bexarotene, reversed cognitive deficits regardless of treatment duration and age in murine models of AD. While bexarotene demonstrated marked efficacy in decreasing plaque levels following short-term treatment, prolonged treatment did not modulate plaque burden...
February 15, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29448852/memantine-in-japanese-patients-with-moderate-to-severe-alzheimer-s-disease-meta-analysis-of-multiple-index-responder-analyses
#20
Kaoru Okuizumi, Teruyoshi Kamata, Daiju Matsui, Kengo Saito, Takuyuki Matsumoto, Yoshikazu Fukuchi
BACKGROUND: Responder analyses assessing clinical worsening have attempted to clarify clinically meaningful drug efficacy enhancements in patients with Alzheimer's disease (AD). RESEARCH DESIGN AND METHODS: This was a meta-analysis of two multicenter, randomized, double-blind, parallel-group, 24-week studies of 633 Japanese patients with moderate to severe AD receiving memantine 20 mg/day (n = 318) or placebo (n = 315). The clinical trial registration number is UMIN000026013...
February 16, 2018: Expert Opinion on Pharmacotherapy
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