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https://www.readbyqxmd.com/read/28527218/the-mechanisms-of-action-of-curcumin-in%C3%A2-alzheimer-s-disease
#1
Mengxi Tang, Changiz Taghibiglou
Alzheimer's disease (AD) is a neurodegenerative disorder of the elderly. As the prevalence of AD rises in the 21st century, there is an urgent need for the development of effective pharmacotherapies. Currently, drug treatments target the symptoms of the disease and do not modify or halt the disease progress. Thus, natural compounds have been investigated for their ability to treat AD. This review examines the efficacy of curcumin, a polyphenol derived from turmeric herb, to treat AD. We summarize the in vivo and in vitro research describing the mechanisms of action in which curcumin modifies AD pathology: curcumin inhibits the formation and promotes the disaggregation of amyloid-β plaques, attenuates the hyperphosphorylation of tau and enhances its clearance, binds copper, lowers cholesterol, modifies microglial activity, inhibits acetylcholinesterase, mediates the insulin signaling pathway, and is an antioxidant...
May 17, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28527217/protein-phosphorylation-is-a-key-mechanism-in-alzheimer-s-disease
#2
Joana Oliveira, Márcio Costa, Maria Soares Cachide de Almeida, Odete A B da Cruz E Silva, Ana Gabriela Henriques
Altered protein phosphorylation states of several proteins are closely associated with Alzheimer's disease (AD). Among these are the amyloid-β precursor protein (AβPP) and the tau protein. In fact, altered protein phosphorylation states already provide strong biomarkers for AD diagnosis, as is the case with hyperphosphorylated tau. It follows that modulating signaling cascades provides an attractive avenue for exploring novel therapeutic strategies. This review focuses on some of the major protein kinases and protein phosphatases relevant to AD...
May 17, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28527210/cerebrospinal-fluid-biomarkers-and-clinical-progression-in-patients-with-subjective-cognitive-decline-and-mild-cognitive-impairment
#3
Steffen Wolfsgruber, Alexandra Polcher, Alexander Koppara, Luca Kleineidam, Lutz Frölich, Oliver Peters, Michael Hüll, Eckart Rüther, Jens Wiltfang, Wolfgang Maier, Johannes Kornhuber, Piotr Lewczuk, Frank Jessen, Michael Wagner
BACKGROUND: There is very limited data on the prevalence of abnormal cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) and their predictive value for clinical progression in memory clinic patients with subjective cognitive decline (SCD). OBJECTIVE: To assess the frequency of abnormal CSF biomarkers of AD and their predictive value for clinical progression in memory clinic patients with SCD in comparison to patients with mild cognitive impairment (MCI) from the same cohort...
May 13, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28527106/a-trans-acting-factor-may-modify-age-at-onset-in-familial-amyloid-polyneuropathy-attrv30m-in-portugal
#4
Miguel Alves-Ferreira, Teresa Coelho, Diana Santos, Jorge Sequeiros, Isabel Alonso, Alda Sousa, Carolina Lemos
Although all familial amyloid polyneuropathy (FAP) ATTRV30M patients carry the same causative mutation, early (<40) and late-onset forms (≥50 years) of FAP may coexist in the same family. However, this variability in age at onset is still unexplained. To identify modifiers closely linked to the TTR locus that may in part be associated with age at onset of FAP ATTRV30M, in particular in a group of very early-onset patients (≤30 years) when compared with late-onset individuals. A clinical genetic study at a referral center comprising a sample of 910 Portuguese individuals includes 589 Val30Met carriers, 102 spouses, and 189 controls from the general population...
May 19, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28527045/amyotrophic-lateral-sclerosis-like-superoxide-dismutase-1-proteinopathy-is-associated-with-neuronal-loss-in-parkinson-s-disease-brain
#5
Benjamin G Trist, Katherine M Davies, Veronica Cottam, Sian Genoud, Richard Ortega, Stéphane Roudeau, Asuncion Carmona, Kasun De Silva, Valerie Wasinger, Simon J G Lewis, Perminder Sachdev, Bradley Smith, Claire Troakes, Caroline Vance, Christopher Shaw, Safa Al-Sarraj, Helen J Ball, Glenda M Halliday, Dominic J Hare, Kay L Double
Neuronal loss in numerous neurodegenerative disorders has been linked to protein aggregation and oxidative stress. Emerging data regarding overlapping proteinopathy in traditionally distinct neurodegenerative diseases suggest that disease-modifying treatments targeting these pathological features may exhibit efficacy across multiple disorders. Here, we describe proteinopathy distinct from classic synucleinopathy, predominantly comprised of the anti-oxidant enzyme superoxide dismutase-1 (SOD1), in the Parkinson's disease brain...
May 19, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28527044/endocytic-vesicle-rupture-is-a-conserved-mechanism-of-cellular-invasion-by-amyloid-proteins
#6
William P Flavin, Luc Bousset, Zachary C Green, Yaping Chu, Stratos Skarpathiotis, Michael J Chaney, Jeffrey H Kordower, Ronald Melki, Edward M Campbell
Numerous pathological amyloid proteins spread from cell to cell during neurodegenerative disease, facilitating the propagation of cellular pathology and disease progression. Understanding the mechanism by which disease-associated amyloid protein assemblies enter target cells and induce cellular dysfunction is, therefore, key to understanding the progressive nature of such neurodegenerative diseases. In this study, we utilized an imaging-based assay to monitor the ability of disease-associated amyloid assemblies to rupture intracellular vesicles following endocytosis...
May 19, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28526839/fluorescence-correlation-spectroscopy-reveals-a-cooperative-unfolding-of-monomeric-amyloid-%C3%AE-42-with-a-low-gibbs-free-energy
#7
Mario Schneider, Stefan Walta, Chris Cadek, Walter Richtering, Dieter Willbold
The amyloid-beta peptide (Aβ) plays a major role in the progression of Alzheimer's disease. Due to its high toxicity, the 42 amino acid long isoform Aβ42 has become of considerable interest. The Aβ42 monomer is prone to aggregation down to the nanomolar range which makes conventional structural methods such as NMR or X-ray crystallography infeasible. Conformational information, however, will be helpful to understand the different aggregation pathways reported in the literature and will allow to identify potential conditions that favour aggregation-incompetent conformations...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28526838/thioflavin-t-fluoresces-as-excimer-in-highly-concentrated-aqueous-solutions-and-as-monomer-being-incorporated-in-amyloid-fibrils
#8
Anna I Sulatskaya, Andrey V Lavysh, Alexander A Maskevich, Irina M Kuznetsova, Konstantin K Turoverov
Fluorescence of thioflavin T (ThT) is a proven tool for amyloid fibrils study. The correct model of ThT binding to fibrils is crucial to clarify amyloid fibrils structure and mechanism of their formation. Although there are convincing evidences that ThT has molecular rotor nature, implying it's binding to fibrils in monomer form, speculations concerning ThT binding to fibrils in aggregated forms appear in literature so far. The elaborated approach for fluorescence intensity correction on the inner filter effects applied to ThT aqueous solutions with a wide range of concentration allowed characterizing ThT excimers fluorescence and showing its difference from that of ThT bound to fibrils...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28526617/cyclin-dependent-kinase-5-a-novel-avenue-for-alzheimer-s-disease
#9
REVIEW
Anisha S Bhounsule, Lokesh Kumar Bhatt, Kedar S Prabhavalkar, Manisha Oza
Alzheimer's disease (AD) is one of the most frequently encountered diseases in adults with progressive loss of memory and behavioural changes. Inspite of there being an intense research in the field of AD, only a few chemical entities exhibiting anti-AD activity make it through the clinical trials and it is thus need of an hour to develop new drugs or repurpose the existing ones for better management of Alzheimer's disease. Novel therapeutic targets can influence drug discovery in the field of AD. Cyclin Dependent Kinase 5 (Cdk5) which is a serine/threonine kinase can prove to be an upcoming beneficial target to be studied for treating AD...
May 16, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28526573/transcriptomic-variation-of-locally-infected-skin-of-epinephelus-coioides-reveals-the-mucosal-immune-mechanism-against-cryptocaryon-irritans
#10
Yazhou Hu, Anxing Li, Yang Xu, Biao Jiang, Geling Lu, Xiaochun Luo
Fish skin is the largest immunologically active mucosal organ, providing first-line defense against external pathogens. However, the skin-associated immune mechanisms of fish are still unclear. Cryptocaryon irritans is an obligate ectoparasitic ciliated protozoan that infects almost all marine fish, and is believed to be an excellent pathogen model to study fish mucosal immunity. In this study, a de novo transcriptome assembly of Epinephelus coioides skin post C. irritans tail-infection was performed for the first time using the Illumina HiSeq™ 2500 system...
May 16, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28526436/intracranial-il-17a-overexpression-decreases-cerebral-amyloid-angiopathy-by-upregulation-of-abca1-in-an-animal-model-of-alzheimer-s-disease
#11
Junling Yang, Jinghong Kou, Robert Lalonde, Ken-Ichiro Fukuchi
Neuroinflammation is a pervasive feature of Alzheimer's disease (AD) and characterized by activated microglia, increased proinflammatory cytokines and/or infiltrating immune cells. T helper 17 (Th17) cells are found in AD brain parenchyma and interleukin-17A (IL-17A) is identified around deposits of aggregated amyloid β protein (Aβ). However, the role of IL-17A in AD pathogenesis remains elusive. We overexpressed IL-17A in an AD mouse model via recombinant adeno-associated virus serotype 5 (rAAV5)-mediated intracranial gene delivery...
May 16, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28526325/expression-of-megf10-in-cholinergic-and-glutamatergic-neurons
#12
Yu Fujita, Tomoji Maeda, Koji Kamaishi, Rui Saito, Koyo Chiba, Xuefeng Shen, Kun Zou, Hiroto Komano
Multiple-EGF like domains 10 (MEGF10) is the mammalian homologue of Draper, a Drosophila phagocytosis receptor that plays an important role in synapse elimination and cell type-specific recognition. However, the expression and function of MEGF10 in the brain remain to be elucidated. Therefore, we aimed to clarify the regions and types of neurons that express MEGF10 in the brain, and to determine whether cells expressing MEGF10 possess phagocytic abilities. Our results indicated that MEGF10 is expressed in cholinergic and glutamatergic neurons of the cortex, hippocampus, and substantia nigra...
May 16, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28524828/relationships-of-inflammatory-factors-and-risk-factors-with-different-target-organ-damage-in-essential-hypertension-patients
#13
Chun-Lin Lai, Jin-Ping Xing, Xiao-Hong Liu, Jie Qi, Jian-Qiang Zhao, You-Rui Ji, Wu-Xiao Yang, Pu-Juan Yan, Chun-Yan Luo, Lu-Fang Ruan
BACKGROUND: Atherosclerosis (AS) is an inflammatory disease. Inflammation was considered to play a role in the whole process of AS. This study aimed to analyze the relationships of inflammatory factors and risk factors with different target organ damages (TOD) in essential hypertension (EH) patients and to explore its clinical significance. METHODS: A total of 294 EH patients were selected and divided into four groups according to their conditions of TOD. Forty-eight healthy subjects were selected as control...
June 5, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28524240/potential-serum-biomarkers-associated-with-mild-and-severe-leptospirosis-infection-a-cohort-study-in-the-malaysian-population
#14
Tan Xue Ting, Fairuz Binti Amran, Ravindran Thayan, Norazah Ahmad, Roslinda Jaafar, Rahimah Haron, Rafidah Abdullah, Sazwan Reezal Bin Shamsuddin, Nor Suhaila Binti Md Riffin, Puteri Shafinaz Abdul-Rahman
Leptospirosis is an emerging zoonotic infectious disease in Malaysia. The symptoms of leptospirosis vary from mild non-specific flu-like illness to a severe condition which is usually associated with serious complication and fatality. To study the protein expression profile of mild and severe leptospirosis, fifteen paired sera were collected from the patients who were mildly infected and following that progressed to severe stage. The proteome profiles of mild and severe cases were studied using 2DE analysis in combination with LC-MS/MS...
May 19, 2017: Electrophoresis
https://www.readbyqxmd.com/read/28524190/establishing-the-link-between-fibril-formation-and-raman-optical-activity-spectra-of-insulin
#15
Jiří Kessler, Shigeki Yamamoto, Petr Bouř
Folding of proteins into insoluble amyloidal fibrils is implicated in a number of biological processes. Optical spectroscopy represents a convenient tool to monitor such structural variations. Recently, characteristic changes in Raman optical activity (ROA) spectra of insulin during a pre-fibrillar stage were reported but not supported by a theoretical model. In the present study, molecular dynamics and the density functional theory are used to simulate the spectra and understand the connection between the structure, and ROA and Raman spectral intensities...
May 19, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28523718/does-sleep-disturbance-affect-the-amyloid-clearance-mechanisms-in-alzheimer-s-disease
#16
REVIEW
Burak Yulug, Lutfu Hanoglu, Ertugrul Kilic
Sleep is one of the important factors that play a key role in AD pathogenesis. However, it is still unclear whether poor quality sleep may overlap with sleep disturbances in the underlying dysfunctional mechanisms of amyloid beta (Aβ) clearance metabolism. Here, we aimed to evaluate the current evidence on the role of sleep deprivation in amyloid beta (Aβ) clearance metabolism. To that end, we discussed possible mechanisms underlying the bidirectional interaction between the sleep deprivation and amyloid beta (Aβ) clearance pathways...
May 18, 2017: Psychiatry and Clinical Neurosciences
https://www.readbyqxmd.com/read/28523576/proteomic-analysis-of-serum-amyloid-a-as-a-potential-marker-in-intestinal-beh%C3%A3-et-s-disease
#17
Hyun Jung Lee, Jae Hyun Kim, Seung Won Kim, Hyun Ah Joo, Hye Won Lee, You Sun Kim, Soo Jung Park, Sung Pil Hong, Tae Il Kim, Won Ho Kim, Young-Ho Kim, Jae Hee Cheon
BACKGROUND/AIMS: Data regarding biomarkers to understand disease pathogenesis and to assess disease activity of intestinal Behçet's disease (BD) are limited. Therefore, we aimed to investigate the differentially expressed proteins in sera from patients with intestinal BD and to search for biomarkers using mass spectrometry-based proteomic analysis. METHODS: Serum samples were pooled for the screening study, and two-dimensional electrophoresis (2-DE) was performed to characterize the proteins present in intestinal BD patients...
May 18, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28523372/dietary-eicosapentaenoic-acid-normalizes-hippocampal-omega-3-and-6-polyunsaturated-fatty-acid-profile-attenuates-glial-activation-and-regulates-bdnf-function-in-a-rodent-model-of-neuroinflammation-induced-by-central-interleukin-1%C3%AE-administration
#18
Yilong Dong, Min Xu, Allan V Kalueff, Cai Song
PURPOSE: Interleukin (IL)-1β can activate glial cells to trigger neuroinflammation and neurodegeneration. Lower omega (n)-3 polyunsaturated fatty acids (PUFAs) and lower n-3/n-6 PUFA ratios occur in the brain of patients with Alzheimer's disease (AD). We have previously reported that an n-3 PUFA, eicosapentaenoic acid (EPA), can improve memory and attenuate neurodegeneration-like changes in animal models of AD. However, whether and how EPA modulates glial cell activity and functions remains unclear...
May 18, 2017: European Journal of Nutrition
https://www.readbyqxmd.com/read/28523319/amyloidosis-a-rare-cause-of-refractory-heart-failure-in-a-young-female
#19
Irina Iuliana Costache, Claudia Florida Costea, Mihai Danciu, Victor Vlad Costan, Viviana Aursulesei, Gabriela FlorenŢa Dumitrescu, Mihaela Dana Turliuc, Anca Sava
Cardiac amyloidosis may occur in any type of systemic amyloidosis. The clinical picture is often characterized by restrictive cardiomyopathy. We report the case of a 41-year-old female patient admitted to the Department of Cardiology with clinical signs of right heart failure: congested jugular veins, hepatomegaly, peripheral edema, ascites associated with atrial fibrillation, low values of arterial blood pressure and oliguria. Echocardiographic findings were helpful for the diagnosis of cardiac amyloidosis: enlarged atrial cavities, normal size ventricles, thickened ventricular septum and posterior left ventricle wall with normal left ventricular ejection fraction, mitral and tricuspid regurgitation...
2017: Romanian Journal of Morphology and Embryology, Revue Roumaine de Morphologie et Embryologie
https://www.readbyqxmd.com/read/28523253/cell-therapy-products-in-alzheimer-disease
#20
REVIEW
Hyeon Jin Song, Tae-Hee Kim, Hae-Hyeog Lee, Jun-Mo Kim, Yoo Jin Park, Arum Lee, Soo Ah Kim, Hye Ji Choi
We are rapidly becoming an aging society, with the ongoing increase in challenges of the elderly. The age-related cognitive decline in accordance with aging society is of major importance in public health. Recent studies have proved the impacts of sex-steroid hormone on the brain; compliant with aging, menopause and decrease in estrogen have an effect on the occurrence and prevention of Alzheimer's disease. A new hypothesis states that Alzheimer's disease is a postmenopausal dementia, and is a negative form of estrogen deficiency...
April 2017: Journal of Menopausal Medicine
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