Database : MEDLINE
Search on : alzheimer and disease [Words]
References found : 132570 [refine]
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[PMID]: 29524731
[Au] Autor:Kumar D; Gupta SK; Ganeshpurkar A; Gutti G; Krishnamurthy S; Modi G; Singh SK
[Ad] Address:Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi 221005, India.
[Ti] Title:Development of Piperazinediones as dual inhibitor for treatment of Alzheimer's disease.
[So] Source:Eur J Med Chem;150:87-101, 2018 Feb 27.
[Is] ISSN:1768-3254
[Cp] Country of publication:France
[La] Language:eng
[Ab] Abstract:Novel multifunctional 3,6-Diphenyl-1,4-bis(phenylsulfonyl)piperazine-2,5-dione derivatives were designed and synthesized for the treatment of Alzheimer's disease (AD). The designed scaffold has blood brain barrier penetrating ability, acetylcholinesterase (AChE) and matrix metalloproteinase-2 (MMP-2) inhibition potential. Compounds 52 and 46 showed very significant inhibition against AChE, IC = 32.45  0.044, 28.65  0.029, BuChE, IC = 157.95  0.264, 160.58  0.082 and MMP-2, IC = 36.83  0.015, 19.57  0.005 (nM). In the enzyme kinetics study, lead molecule 46 showed non-competitive inhibition of AChE with K = 7 nM and competitive inhibition of MMP-2 with K = 20 nM. Compounds 52 and 46 inhibited AChE-induced A aggregation at 20 M. The compounds also exhibited in-vitro antioxidant potential in DPPH assay. Further, compound 46 was found to be a promising neuroprotective agent in MC65 cells. Lead molecule 46 significantly enhanced working memory in scopolamine induced amnesia animal model at dose of 5 mg/kg dose. The mitochondrial membrane potential was restored in animals when treated with compounds 52 and 46.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher

  2 / 132570 MEDLINE  
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[PMID]: 29524596
[Au] Autor:Liu KY; Stringer AE; Reeves SJ; Howard RJ
[Ad] Address:Division of Psychiatry, University College London, UK. Electronic address: kathy.liu@ucl.ac.uk.
[Ti] Title:The neurochemistry of agitation in Alzheimer's disease: a systematic review.
[So] Source:Ageing Res Rev;, 2018 Mar 07.
[Is] ISSN:1872-9649
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:OBJECTIVE: To provide an up-to-date systematic review of the characteristics, methodology and findings of studies that have investigated the neurochemistry of agitation in Alzheimer's disease (AD). METHODS: Electronic databases were searched for published peer-reviewed articles which provided data on any neurotransmitter system in relation to agitation in AD. Screening of titles and abstracts and data extraction from full texts were conducted in duplicate. RESULTS: Forty-five studies were included. Monoamines (serotonin, dopamine and noradrenaline) were most commonly investigated. A variety of methods were used to investigate the neurochemistry underlying agitation in AD and, although there were several conflicting findings, there was evidence of serotonergic deficit, relatively preserved dopaminergic function and compensatory overactivity of postsynaptic noradrenergic neurons in agitation in AD. CONCLUSIONS: Disruption of the dynamic balance between multiple neurotransmitter systems could impair functional neural networks involved in affective regulation and executive function. Differences in study design and methodology may have contributed to conflicting findings. Future studies that overcome these limitations (e.g. using standardized criteria to define agitation) and employ neuroimaging methods such as MRI/PET to investigate specific neural networks are needed to clarify the role of neurotransmitter alterations in these patients.
[Pt] Publication type:JOURNAL ARTICLE; REVIEW
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher

  3 / 132570 MEDLINE  
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[PMID]: 29524561
[Au] Autor:Timmermans JP
[Ad] Address:Laboratory of Cell Biology & Histology, Department of Veterinary Sciences, University of Antwerp, Universiteitsplein 1, BE 2610 Wilrijk, Belgium. Electronic address: jean-pierre.timmermans@uantwerpen.be.
[Ti] Title:Need for more holistic therapeutic and management strategies to understand the causal or correlative link of the A amyloid pathway with Alzheimer's disease for a more efficint treatment.
[So] Source:Peptides;, 2018 Mar 07.
[Is] ISSN:1873-5169
[Cp] Country of publication:United States
[La] Language:eng
[Pt] Publication type:EDITORIAL
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher

  4 / 132570 MEDLINE  
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[PMID]: 29524490
[Au] Autor:Li Y; Guan S; Liu C; Chen X; Zhu Y; Xie Y; Wang J; Ji X; Li L; Li Z; Zhang Y; Zeng X; Li M
[Ad] Address:Department of Traditional Chinese Medicine, Shanghai Pudong Hopstital, Fudan University Pudong Medical Center, Shanghai 201399, China; Chuangchun University of Chinese Medicine, Changchun, Jilin 130117, China.
[Ti] Title:Neuroprotective effects of Coptis chinensis Franch polysaccharide on amyloid-beta (A)-induced toxicity in a transgenic Caenorhabditis elegans model of Alzheimer's disease (AD).
[So] Source:Int J Biol Macromol;, 2018 Mar 07.
[Is] ISSN:1879-0003
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:This study aims to investigate the neuroprotective effects of Coptis chinensis Franch polysaccharide (CCP) on A transgenic CL4176 Caenorhabditis elegans, as well as its mechanism of action. The results in life span experiment showed that CCP could significantly increase the lifespan of C. elegans and the effect is in the descending order of 100 mg/L > 500 mg/L > 200 mg/L. The behavioral experiments also demonstrated that CCP at the concentration of 100 mg/L could delay the paralysis rate of C. elegans, which was significantly different from the control group. In terms of A toxicity in C. elegans, morphological observation using Thioflavin S staining method indicated that the deposition of A protein in the head area of the untreated C. elegans was much more than those in the CCP (100 mg/L)-treated CL4176. In line with this finding, fluorogenic quantitative real-time PCR confirmed that the transcriptional levels of HSP16.2 (Y46H3A.D) and HSP16.41 (Y46H3A.E) in C. elegans was 21 times and 79 times higher than those in untreated control. Thus, these data demonstrate that CCP could reduce A-induced toxicity by delaying the aging, decreasing the rate of paralysis, inhibiting the deposition of A, and increasing the expression levels of HSP genes in transgenic C. elegans.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher

  5 / 132570 MEDLINE  
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[PMID]: 29524426
[Au] Autor:Chiba-Falek O; Gottschalk WK; Lutz MW
[Ad] Address:Department of Neurology, Duke University Medical Center, Durham, NC, USA; Center for Genomic and Computational Biology, Duke University Medical Center, Durham, NC, USA. Electronic address: o.chibafalek@duke.edu.
[Ti] Title:The effects of the TOMM40 poly-T alleles on Alzheimer's disease phenotypes.
[So] Source:Alzheimers Dement;, 2018 Mar 07.
[Is] ISSN:1552-5279
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:The TOMM40 poly-T is a polymorphism in intron 6 of the TOMM40 gene, which is adjacent to and in linkage disequilibrium with APOE. Roses etal identified the association between the length of TOMM40 poly-T with the risk and age of onset of late-onset Alzheimer's disease (LOAD). Following the original discovery, additional studies found associations between the TOMM40 poly-T and LOAD-related phenotypes independent of APOE genotypes, while others did not replicate these associations. Furthermore, the identity of the TOMM40 poly-T risk allele has been controversial between different LOAD-related phenotypes. Here, we propose a framework to address the conflicting findings with respect to the TOMM40 poly-T allele associations with LOAD phenotypes and their functional effects. The framework is used to interpret previous studies as means to gain insights regarding the nature of the risk allele, very long versus short. We suggest that the identity of the TOMM40 poly-T risk allele depends on the phenotype being evaluated, the ages of the study subjects at the time of assessment, and the context of the APOE genotypes. In concluding remarks, we outline future studies that will inform the mechanistic interpretation of the genetic data.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher

  6 / 132570 MEDLINE  
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[PMID]: 29512653
[Au] Autor:Scapin G; Dandey VP; Zhang Z; Prosise W; Hruza A; Kelly T; Mayhood T; Strickland C; Potter CS; Carragher B
[Ad] Address:Merck & Co., Inc., Department of Biochemical Engineering & Structure, 2000 Galloping Hill Rd. Kenilworth, NJ, 07033, USA.
[Ti] Title:Structure of the Insulin Receptor-Insulin Complex by Single Particle CryoEM analysis.
[So] Source:Nature;, 2018 Feb 28.
[Is] ISSN:1476-4687
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:The insulin receptor (IR) is a dimeric protein that plays a crucial role in controlling glucose homeostasis, regulating lipid, protein and carbohydrate metabolism, and modulating brain neurotransmitter levels . IR dysfunction has been associated with many diseases, including diabetes, cancer, and Alzheimer's disease . The primary sequence has been known since the 1980s , and is composed of an extracellular portion (ectodomain, ECD), a single transmembrane helix and an intracellular tyrosine kinase domain. Insulin binding to the dimeric ECD triggers kinase domain auto-phosphorylation and subsequent activation of downstream signaling molecules. Biochemical and mutagenesis data have identified two putative insulin binding sites (S1 and S2) . While insulin bound to an ECD fragment containing S1 and the apo ectodomain have been characterized structurally , details of insulin binding to the full receptor and the signal propagation mechanism are still not understood. Here we report single particle cryoEM reconstructions for the 1:2 (4.3 ) and 1:1 (7.4 ) IR ECD dimer:Insulin complexes. The symmetric 4.3 structure shows two insulin molecules per dimer, each bound between the Leucine-rich sub domain L1 of one monomer and the first fibronectin-like domain (FnIII-1) of the other monomer, and making extensive interactions with the α subunit C-terminal helix (α-CT helix). The 7.4 structure has only one similarly bound insulin per receptor dimer. The structures confirm the S1 binding interactions and define the full S2 binding site. These insulin receptor states suggest that recruitment of the α-CT helix upon binding of the first insulin changes the relative subdomain orientations and triggers downstream signal propagation.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180311
[Lr] Last revision date:180311
[St] Status:Publisher
[do] DOI:10.1038/nature26153

  7 / 132570 MEDLINE  
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[PMID]: 29511163
[Au] Autor:Delprat B; Maurice T; Delettre C
[Ad] Address:INSERM UMR-S1198, 34095, Montpellier, France. benjamin.delprat@inserm.fr.
[Ti] Title:Wolfram syndrome: MAMs' connection?
[So] Source:Cell Death Dis;9(3):364, 2018 Mar 06.
[Is] ISSN:2041-4889
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Wolfram syndrome (WS) is a rare neurodegenerative disease, the main pathological hallmarks of which associate with diabetes, optic atrophy, and deafness. Other symptoms may be identified in some but not all patients. Prognosis is poor, with death occurring around 35 years of age. To date, no treatment is available. WS was first described as a mitochondriopathy. However, the localization of the protein on the endoplasmic reticulum (ER) membrane challenged this hypothesis. ER contacts mitochondria to ensure effective Ca transfer, lipids transfer, and apoptosis within stabilized and functionalized microdomains, termed "mitochondria-associated ER membranes" (MAMs). Two types of WS are characterized so far and Wolfram syndrome type 2 is due to mutation in CISD2, a protein mostly expressed in MAMs. The aim of the present review is to collect evidences showing that WS is indeed a mitochondriopathy, with established MAM dysfunction, and thus share commonalities with several neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, as well as metabolic diseases, such as diabetes.
[Pt] Publication type:JOURNAL ARTICLE; REVIEW
[Em] Entry month:1803
[Cu] Class update date: 180311
[Lr] Last revision date:180311
[St] Status:In-Data-Review
[do] DOI:10.1038/s41419-018-0406-3

  8 / 132570 MEDLINE  
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[PMID]: 29510747
[Au] Autor:Franzmeier N; Hartmann J; Taylor ANW; Araque-Caballero M; Simon-Vermot L; Kambeitz-Ilankovic L; Brger K; Catak C; Janowitz D; Mller C; Ertl-Wagner B; Stahl R; Dichgans M; Duering M; Ewers M
[Ad] Address:Institute for Stroke and Dementia Research, Klinikum der Universitt Mnchen, Ludwig-Maximilians-Universitt (LMU), Feodor-Lynen Strae 17, 81377, Munich, Germany.
[Ti] Title:The left frontal cortex supports reserve in aging by enhancing functional network efficiency.
[So] Source:Alzheimers Res Ther;10(1):28, 2018 Mar 06.
[Is] ISSN:1758-9193
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:BACKGROUND: Recent evidence derived from functional magnetic resonance imaging (fMRI) studies suggests that functional hubs (i.e., highly connected brain regions) are important for mental health. We found recently that global connectivity of a hub in the left frontal cortex (LFC connectivity) is associated with relatively preserved memory abilities and higher levels of protective factors (education, IQ) in normal aging and Alzheimer's disease. These results suggest that LFC connectivity supports reserve capacity, alleviating memory decline. An open question, however, is why LFC connectivity is beneficial and supports memory function in the face of neurodegeneration. We hypothesized that higher LFC connectivity is associated with enhanced efficiency in connected major networks involved in episodic memory. We further hypothesized that higher LFC-related network efficiency predicts higher memory abilities. METHODS: We assessed fMRI during a face-name association learning task performed by 26 healthy, cognitively normal elderly participants. Using beta-series correlation analysis, we computed task-related LFC connectivity to key memory networks, including the default mode network (DMN) and dorsal attention network (DAN). Network efficiency within the DMN and DAN was estimated by the graph theoretical small-worldness statistic. We applied linear regression analyses to test the association between LFC connectivity with the DMN/DAN and small-worldness of these networks. Mediation analysis was applied to test LFC connectivity to the DMN and DAN as a mediator of the association between education and higher DMN and DAN small-worldness. Last, we tested network small-worldness as a predictor of memory performance. RESULTS: We found that higher LFC connectivity to the DMN and DAN during successful memory encoding and recognition was associated with higher small-worldness of those networks. Higher task-related LFC connectivity mediated the association between education and higher small-worldness in the DMN and DAN. Further, higher small-worldness of these networks predicted better performance in the memory task. CONCLUSIONS: The present results suggest that higher education-related LFC connectivity to key memory networks during a memory task is associated with higher network efficiency and thus enhanced reserve of memory abilities in aging.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180311
[Lr] Last revision date:180311
[St] Status:In-Data-Review
[do] DOI:10.1186/s13195-018-0358-y

  9 / 132570 MEDLINE  
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[PMID]: 29494806
[Au] Autor:Ovsepian SV; O'Leary VB; Zaborszky L; Ntziachristos V; Dolly JO
[Ad] Address:Institute for Biological and Medical Imaging, Helmholtz Zentrum Munich, German Research Center for Environmental Health, Neuherberg, Germany; Munich School of Bioengineering, Technical University Munich, Munich, Germany; International Centre for Neurotherapeutics, Dublin City University, Dublin, Ire
[Ti] Title:Synaptic vesicle cycle and amyloid : Biting the hand that feeds.
[So] Source:Alzheimers Dement;, 2018 Mar 01.
[Is] ISSN:1552-5279
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:The synaptic vesicle cycle (SVC) holds center stage in the biology of presynaptic terminals. Through recurrent exocytosis and endocytosis, it facilitates a sequence of events enabling chemical neurotransmission between functionally related neurons. As a fundamental process that links the interior of nerve cells with their environment, the SVC is also critical for signaling and provides an entry route for a range of pathogens and toxins, enabling detrimental effects. In Alzheimer's disease, the SVC is both the prime site of amyloid production and toxicity. In this study, we discuss the emerging evidence for physiological and pathological effects of A on various stages of the SVC, from postfusion membrane recovery to trafficking, docking, and priming of vesicles for fusion and transmitter release. Understanding of the mechanisms of A interaction with the SVC within the unifying calcium hypothesis of aging and Alzheimer's disease should further elucidate the fundamental biology of the presynaptic terminal and reveal novel therapeutic targets for Alzheimer's disease and other age-related dementias.
[Pt] Publication type:JOURNAL ARTICLE; REVIEW
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher

  10 / 132570 MEDLINE  
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[PMID]: 29486288
[Au] Autor:Di Natale C; Monaco A; Pedone C; Tessitore A; De Mase A; Tedeschi G; Netti PA; Abrescia P
[Ad] Address:Department of Biology, University of Naples Federico II, via Mezzocannone 8, 80134 Naples, Italy. Electronic address: concetta.dinatale@unina.it.
[Ti] Title:The level of 24-hydroxycholesteryl esters decreases in plasma of patients with Parkinson's disease.
[So] Source:Neurosci Lett;672:108-112, 2018 Feb 24.
[Is] ISSN:1872-7972
[Cp] Country of publication:Ireland
[La] Language:eng
[Ab] Abstract:24-hydroxycholesterol (24OH-C) is synthesized almost exclusively in neurons. This oxysterol is mostly present as ester form in both cerebrospinal fluid and plasma. The enzyme lecithin-cholesterol acyltransferase esterifies 24OH-C in the brain, and the level of 24OH-C esters in cerebrospinal fluid was found to be correlated with the level of 24OH-C esters in plasma. Decreased levels of 24OH-C esters levels were previously found in Alzheimer's disease and Amyotrophic Lateral Sclerosis. This finding was attributed to the inhibitory effect of oxidative stress on lecithin-cholesterol acyltransferase activity in neurodegenerative conditions. Data reported here show that the plasma level of 24OH-C esters is decreased also in Parkinson's disease. ROC analysis identified 69.0% of 24OH-C esterification as the threshold (AUC = 0.98) discriminating patients (N = 19) from healthy subjects (N = 19) with 100% specificity vs controls, 89.5% sensitivity, 94.7% accuracy, and 100% precision. The level of 24OH-C esters was not correlated with UPDRS I or UPDRS III when evaluated at the time of blood sampling. By contrast, it was negatively correlated with UPDRS I (r = -0.4984, p = 0.0299) after one year of follow up. Therefore, this level might represent a novel biomarker of neurodegeneration in Parkinson's disease. The biomarker level is here proposed as a measure to evaluate the severity of disease, as well as to monitor the progression of this pathology.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher


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