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Meaghann S Weaver, Brittany Wichman, Sue Bace, Denice Schroeder, Catherine Vail, Chris Wichman, Andrew Macfadyen
The national nursing shortage translates into a gap in home nursing care available to children with complex, chronic medical conditions and their family caregivers receiving palliative care consultations. A total of 38 home health nursing surveys were completed by families receiving pediatric palliative care consultation services at a freestanding children's hospital in the Midwest. The gap in the average number of nursing hours allotted versus received was 40 h/wk per family, primarily during evening hours...
June 2018: Journal of Hospice and Palliative Nursing: JHPN
Guilin Meng, Xiulin Meng, Xiaoye Ma, Gengping Zhang, Xiaolin Hu, Aiping Jin, Yanxin Zhao, Xueyuan Liu
Alzheimer's disease (AD) is an increasing concern in human health. Despite significant research, highly effective drugs to treat AD are lacking. The present study describes the text mining process to identify drug candidates from a traditional Chinese medicine (TCM) database, along with associated protein target mechanisms. We carried out text mining to identify literatures that referenced both AD and TCM and focused on identifying compounds and protein targets of interest. After targeting one potential TCM candidate, corresponding protein-protein interaction (PPI) networks were assembled in STRING to decipher the most possible mechanism of action...
2018: Frontiers in Neuroinformatics
Qing-Hua Yang, Ling Guo, Qing Chen, Kai-Hui Wu, Yan-Jun Wu, Yan Jia, Shu-Juan Zhu, Cheng-Lin Tang, Hua-Jun Sheng
OBJECTIVE: To observe the effect of electroacupuncture (EA) intervention on learning-memory ability and the expression of senile plaques (SP), amyloid precursor protein (APP), β-secretase 1(BACE 1) and insulin degrading enzyme (IDE) in the hippocampus in APP/presenilin 1 (PS 1) double transgenic Alzheimer's disease (AD) mice, so as to reveal its mechanisms underlying improvement of AD. METHODS: A total of 18 male APP/PS 1 double transgenic AD mice were randomly divided into model, EA-2-week and EA-3-week groups ( n =6 in each)...
April 25, 2018: Zhen Ci Yan Jiu, Acupuncture Research
Vladimir Volloch, Sophia Rits
The present review analyzes the results of recent clinical trials of β secretase inhibition in sporadic Alzheimer's disease (SAD), considers the striking dichotomy between successes in tests of β-site Amyloid Precursor Protein-Cleaving Enzyme (BACE) inhibitors in healthy subjects and familial Alzheimer's disease (FAD) models versus persistent failures of clinical trials and interprets it as a confirmation of key predictions for a mechanism of amyloid precursor protein (APP)-independent, β secretase inhibition-resistant production of β amyloid in SAD, previously proposed by us...
June 2, 2018: Medical Sciences: Open Access Journal
Asher Mullard
No abstract text is available yet for this article.
May 30, 2018: Nature Reviews. Drug Discovery
Diana Scholz, Yana Chernyshova, Anna-Katharina Ückert, Marcel Leist
The initial step in the amyloidogenic cascade of amyloid precursor protein (APP) processing is catalyzed by beta-site APP-cleaving enzyme (BACE), and this protease has increased activities in affected areas of Alzheimer's disease brains. We hypothesized that altered APP processing, due to augmented BACE activity, would affect the actions of direct and indirect BACE inhibitors. We therefore compared postmitotic human neurons (LUHMES) with their BACE-overexpressing counterparts (BLUHMES). Although β-cleavage of APP was strongly increased in BLUHMES, they produced less full-length and truncated amyloid beta (Aβ) than LUHMES...
May 27, 2018: Journal of Neurochemistry
Jian Yang, Jing Yang, Yuyan Li, Yungen Xu, Chongzhao Ran
PURPOSE: Near-infrared fluorescence (NIRF) imaging has been widely used in preclinical studies; however, its low tissue penetration represents a daunting problem for translational clinical imaging of neurodegenerative diseases. The retina is known as an extension of the central nerve system (CNS), and it is widely considered as a window to the brain. Therefore, the retina can be considered as an alternative organ for investigating neurodegenerative diseases, and an eye represents an ideal NIRF imaging organ, due to its minimal opacity...
May 25, 2018: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
Yang Ruan, Shi-Jie Guo, Xu Wang, Dong Dong, Dong-Hui Shen, Jie Zhu, Xiang-Yu Zheng
Kainic acid (KA) was recently identified as an epileptogenic and neuroexcitotoxic agent that is responsible for inducing learning and memory deficits in various neurodegenerative diseases, such as Alzheimer's disease (AD). However, the mechanism by which KA acts upon AD remains unclear. To this end, we presently investigated the roles of KA in processing amyloid-β protein precursor (AβPP) and amyloid-β protein (Aβ) loads during the course of AD development and progression. Specifically, KA treatment clearly caused the upregulation of tumor necrosis factor α (TNF-α) via activation of the PI3-K/AKT, ERK1/2, and p65 pathways in glial cells...
May 16, 2018: Journal of Alzheimer's Disease: JAD
Vinothkumar G, Krishnakumar S, Sureshkumar, Shivashekar G, Sreedhar S, Preethikrishnan, Dinesh S, Sundaram A, Balakrishnan D, Riya, Venkataraman P
BACKGROUND: Cognitive dysfunction is reported to be a major cause of morbidity in chronic kidney disease (CKD). The senile plaques (SPs) in the brain are one of the most pathophysiological characteristics of cognitive dysfunction and its major constituent amyloid β (Aβ) released from amyloid precursor protein (APP) by β (BACE1) and γ (presenilin 1) secretases . Platelets contain more than 95% of the circulating APP and implicate as a candidate biomarker for cognitive decline. Recombinant human erythropoietin (rHuEPO) is a standard therapy for anemia in CKD and also acts as a neuroprotective agent...
August 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Syed Haris Omar, Christopher J Scott, Adam S Hamlin, Hassan K Obied
The focus of this study was on inhibition of enzymes involved in the pathogenesis Alzheimer's disease (AD) including prime amyloid beta (Aβ) producing enzyme (β-secretase: BACE-1) and disease progression enzymes including acetylcholinesterase (AChE), butyrylcholinesterase (BChE), histone deacetylase (HDAC), and tyrosinase along with the catecholamine L-DOPA, by using olive biophenols. Here we report the strongest inhibition of BACE-1 from rutin (IC50 : 3.8 nM) followed by verbascoside (IC50 : 6.3 nM) and olive fruit extract (IC50 : 18 ng), respectively...
May 14, 2018: Fitoterapia
Siem Jakob Veenstra, Heinrich Rueeger, Markus Voegtle, Rainer Lueoend, Philipp Holzer, Konstanze Hurth, Marina Tintelnot-Blomley, Mathias Frederiksen, Jean-Michel Rondeau, Laura Jacobson, Matthias Staufenbiel, Ulf Neumann, Rainer Machauer
New amino-1,4-oxazine derived BACE-1 inhibitors were explored and various synthetic routes developed. The binding mode of the inhibitors was elucidated by co-crystallization of 4 with BACE-1 and X-ray analysis. Subsequent optimization led to inhibitors with low double digit nanomolar activity in a biochemical and single digit nanomolar potency in a cellular assays. To assess the inhibitors for their permeation properties and potential to cross the blood-brain-barrier a MDR1-MDCK cell model was successfully applied...
May 3, 2018: Bioorganic & Medicinal Chemistry Letters
Hao Hu, Haiyan Li, Jieqiong Li, Jintai Yu, Lan Tan
BACKGROUND: The activity of cerebrospinal fluid (CSF) β-site APP cleaving enzyme (BACE) is a potential diagnostic biomarker for Alzheimer disease (AD). METHODS: A total of 340 non-Hispanic Caucasian participants from the Alzheimer's Disease Neuroimaging Initiative cohort (ADNI) database were included in this study with quality-controlled CSF BACE and genotype data. Association of CSF BACE with the genetic variants of single nucleotide polymorphisms (SNPs) was assessed using PLINK under the additive genetic model...
May 11, 2018: BMC Medical Genetics
Jungmi Lee, Annie Agnes Suganya Samson, Joon Myong Song
Amyloid-β (Aβ) is generated by proteolytic processing of amyloid precursor protein (APP) by beta-secretase (BACE-1) and gamma-secretase. Amyloid-β is responsible for the formation of senile plaques in Alzheimer's disease (AD). Consequently, inhibition of β-secretase (BACE-1), a rate-limiting enzyme in the production of Aβ, constitutes an attractive therapeutic approach to the treatment of AD. This paper reports an inkjet printing-based fluorescence assay for high throughput screening of β-secretase inhibitors achieved by employing a BACE-1 FRET substrate (Rh-Glu-Val-Asn-Leu-Asp-Ala-Glu-Phe-Lys-Quencher)...
August 31, 2018: Analytica Chimica Acta
Michael F Egan, James Kost, Pierre N Tariot, Paul S Aisen, Jeffrey L Cummings, Bruno Vellas, Cyrille Sur, Yuki Mukai, Tiffini Voss, Christine Furtek, Erin Mahoney, Lyn Harper Mozley, Rik Vandenberghe, Yi Mo, David Michelson
BACKGROUND: Alzheimer's disease is characterized by the deposition of amyloid-beta (Aβ) plaques in the brain. Aβ is produced from the sequential cleavage of amyloid precursor protein by β-site amyloid precursor protein-cleaving enzyme 1 (BACE-1) followed by γ-secretase. Verubecestat is an oral BACE-1 inhibitor that reduces the Aβ level in the cerebrospinal fluid of patients with Alzheimer's disease. METHODS: We conducted a randomized, double-blind, placebo-controlled, 78-week trial to evaluate verubecestat at doses of 12 mg and 40 mg per day, as compared with placebo, in patients who had a clinical diagnosis of mild-to-moderate Alzheimer's disease...
May 3, 2018: New England Journal of Medicine
Minji Woo, Jeong Sook Noh, Eun Ju Cho, Yeong Ok Song
This study investigated the inhibitory effects of kimchi bioactive compounds against endoplasmic reticulum (ER) stress-induced apoptosis in amyloid beta (Aβ)-injected mice. Mice received a single intracerebroventricular injection of Aβ25-35 , except for the normal group. Mice were subjected to oral administration of 10 mg of capsaicin, 50 mg of 3-(4'-hydroxyl-3',5'-dimethoxyphenyl)propionic acid (HDMPPA), 50 mg of quercetin, 50 mg of ascorbic acid, or 200 mg of kimchi methanol extract (KME) per kilogram of body weight for 2 weeks ( n = 7 per group)...
May 16, 2018: Journal of Agricultural and Food Chemistry
Sneha R Sagar, Devendra Pratap Singh, Nirupa B Panchal, Rajesh D Das, Dhaivat H Pandya, Vasudevan Sudarsanam, Manish Nivsarkar, Kamala K Vasu
Alzheimer's disease (AD) is associated with multiple neuropathological events including β-site amyloid precursor protein cleaving enzyme-1 (BACE-1) inhibition and neuronal inflammation, ensuing degeneracy, and death to neuronal cells. Targeting such a complex disease via a single target directed treatment was found to be inefficacious. Hence, with an intention to incorporate multiple therapeutic effects within a single molecule, multitarget-directed ligands (MTDLs) have been evolved. Herein, for the first time, we report the discovery of novel thiazolyl-thiadiazines that can serve as MTDLs as evident from the in vitro and in vivo studies...
May 10, 2018: ACS Chemical Neuroscience
Eleni Papadopoulou, Jérémie Botton, Anne-Lise Brantsæter, Margaretha Haugen, Jan Alexander, Helle Margrete Meltzer, Jonas Bacelis, Anders Elfvin, Bo Jacobsson, Verena Sengpiel
OBJECTIVES: To study the association between maternal caffeine intake during pregnancy and the child's weight gain and overweight risk up to 8 years. DESIGN: Prospective nationwide pregnancy cohort. SETTING: The Norwegian Mother and Child Cohort Study. PARTICIPANTS: A total of 50 943 mothers recruited from 2002 to 2008 and their children, after singleton pregnancies, with information about average caffeine intake assessed at mid-pregnancy...
April 23, 2018: BMJ Open
Rosanna Caliandro, Alessandro Pesaresi, Luca Cariati, Antonio Procopio, Manuela Oliverio, Doriano Lamba
Acetylcholinesterase inhibitors were introduced for the symptomatic treatment of Alzheimer's disease (AD). Among the currently approved inhibitors, donepezil (DNP) is one of the most preferred choices in AD therapy. The X-ray crystal structures of Torpedo californica AChE in complex with two novel rigid DNP-like analogs, compounds 1 and 2, have been determined. Kinetic studies indicated that compounds 1 and 2 show a mixed-type inhibition against TcAChE, with Ki values of 11.12 ± 2.88 and 29.86 ± 1...
December 2018: Journal of Enzyme Inhibition and Medicinal Chemistry
Jesus Campagna, Kanagasabai Vadivel, Barbara Jagodzinska, Michael Jun, Tina Bilousova, Patricia Spilman, Varghese John
The aspartyl protease BACE1 (BACE) has emerged as an appealing target for reduction of amyloid-β in Alzheimer's disease. The clinical fate of active-site BACE inhibitors may depend on potential side effects related to enzyme and substrate selectivity. One strategy to reduce this risk is through development of allosteric inhibitors that interact with and modulate the Loop F region unique to BACE1. Previously, a BACE-inhibiting antibody (Ab) was shown by co-crystallization to bind and induce conformational changes of Loop F, resulting in backbone perturbations at the distal S6 and S7 subsites, preventing proper binding of a long APP-like substrate to BACE and inhibiting its cleavage...
May 25, 2018: Journal of Molecular Biology
M Asif Taqi, Syed A Quadri, Ajit S Puri, Brian F Fitzsimmons, Jianhua Nancy Jin, Ansaar T Rai, Curtis A Given, Javier Masso, Ciaran J Powers, Joey D English, Osama O Zaidat
Background and Purpose: Adjunctive treatments like balloon-assisted coil embolization (BACE) and stent-assisted coil embolization play a major role in the treatment of wide-neck and large intracranial aneurysms. The TransForm™ Occlusion Balloon Catheter (TOBC) registry is intended to evaluate the safety, efficacy, and efficiency of BACE using the TOBC. Method and Study Design: The TOBC registry is a prospective multicenter registry trial. Seven sites in the USA and 1 site in Spain participated and enrolled 81 patients...
February 2018: Interventional Neurology
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