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Alzheimer's prevention

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https://www.readbyqxmd.com/read/29775277/cid-9998128-compound-is-a-potential-multi-target-drug-for-alzheimer-s-disease
#1
Nguyen Quoc Thai, Zuzana Bednarikova, Miroslav Gancar, Huynh Quang Linh, Chin-Kun Hu, Mai Suan Li, Zuzana Gazova
We have probed capability of small CID 9998128 compound as a potential multi-target drug for the Alzheimer's disease (AD) using in silico and in vitro experiments. By all-atom simulation and MM-PBSA method we have demonstrated that this compound strongly binds to both amyloid beta 42 (Aβ42 ) fibrils and β-secretase and the van der Waals interaction is dominating over the electrostatic interaction in binding affinity. A detailed analysis at the atomic level revealed that indazole in CID 99998128 structure made a major contribution to instability of all studied complexes...
May 18, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29774745/interplay-between-copper-neprilysin-and-n-truncation-of-%C3%AE-amyloid
#2
Mariusz Mital, Wojciech Bal, Tomasz Frączyk, Simon C Drew
Sporadic Alzheimer's disease (AD) is associated with an inefficient clearance of the β-amyloid (Aβ) peptide from the central nervous system. The protein levels and activity of the Zn2+ -dependent endopeptidase neprilysin (NEP) inversely correlate with brain Aβ levels during aging and in AD. The present study considered the ability of Cu2+ ions to inhibit human recombinant NEP and the role for NEP in generating N-truncated Aβ fragments with high-affinity Cu2+ binding motifs that can prevent this inhibition...
May 18, 2018: Inorganic Chemistry
https://www.readbyqxmd.com/read/29774516/periodic-variation-of-aak1-in-an-a%C3%AE-1-42-induced-mouse-model-of-alzheimer-s-disease
#3
Xue Fu, Meiling Ke, Weihua Yu, Xia Wang, Qian Xiao, Min Gu, Yang Lü
Inhibition of endocytosis in an Alzheimer's disease (AD) model has been shown to be able to prevent amyloid β (Aβ)-induced damage and to exert a beneficial effect in treating AD. Adaptor-associated kinase 1 (AAK1), which binds to the adaptor protein complex 2 (AP-2), regulates the process of clathrin-mediated endocytosis. However, how AAK1 expression varies over the course of AD is unknown. In this study, we investigated AAK1 levels in AD model mice over time. Aβ1-42 was used to establish a mouse AD model, and the Morris water maze test was used to characterize the time course of Aβ1-42 -induced cognition changes...
May 17, 2018: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/29773015/caffeine-a-potential-protective-agent-against-cognitive-decline-in-alzheimer-s-disease
#4
Azhar Hussain, Elsa S Tabrez, Volodymyr Mavrych, Olena Bolgova, Jagannadha Rao Peela
Over the past few decades, caffeine has been well recognized as a stimulant whose effects can be detected particularly in the central nervous system. A stimulating effect of caffeine has been found useful in treating patients with many neurological disorders, including Alzheimer's disease (AD). AD is reported to be a rapidly increasing public health problem with lack of a remedial treatment. However, the assumed protective effects of caffeine against AD are of huge interest. This study substantiates caffeine's role as a potential prevention agent against AD through several epidemiological studies...
2018: Critical Reviews in Eukaryotic Gene Expression
https://www.readbyqxmd.com/read/29772745/tryptophan-containing-dual-neuroprotective-peptides-prolyl-endopeptidase-inhibition-and-caenorhabditis-elegans-protection-from-%C3%AE-amyloid-peptide-toxicity
#5
Paloma Manzanares, Roberto Martínez, Sandra Garrigues, Salvador Genovés, Daniel Ramón, Jose F Marcos, Patricia Martorell
Neuroprotective peptides represent an attractive pharmacological strategy for the prevention or treatment of age-related diseases, for which there are currently few effective therapies. Lactoferrin (LF)-derived peptides (PKHs) and a set of six rationally-designed tryptophan (W)-containing heptapeptides (PACEIs) were characterized as prolyl endopeptidase (PEP) inhibitors, and their effect on β-amyloid peptide (Aβ) toxicity in a Caenorhabditis elegans model of Alzheimer's disease (AD) was evaluated. Two LF-derived sequences, PKH8 and PKH11, sharing a W at the C-terminal end, and the six PACEI heptapeptides (PACEI48L to PACEI53L) exhibited significant in vitro PEP inhibition...
May 16, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29772526/marine-derived-bioactive-compounds-for-treatment-of-alzheimer-s-disease
#6
Sreeja Lakshmi, Parvathi Prakash, Musthafa M Essa, Walid M Qoronfleh, Mohammed Akbar, Byoung-Joon Song, Suresh Kumar, Preetham Elumalai
Alzheimer's disease (AD ) is mounting as social and economic encumbrance which are accompanied by deficits in cognition and memory. Over the past decades, Alzheimer's disease (AD) holds the frontline as one of the biggest healthcare issues in the world. AD is an age related neurodegenerative disorder marked by a decline in memory and an impairment of cognition. Inspite of tedious scientific effort, AD is still devoid of pharmacotherapeutic strategies for treatment as well as prevention. Current treatment strategies using drugs are symbolic in nature as they treat disease manifestation though are found effective in treating cognition...
June 1, 2018: Frontiers in Bioscience (Elite Edition)
https://www.readbyqxmd.com/read/29772028/randomized-phase-i-trial-hiv-core-003-depletion-of-serum-amyloid-p-component-and-immunogenicity-of-dna-vaccination-against-hiv-1
#7
Nicola J Borthwick, Thirusha Lane, Nathifa Moyo, Alison Crook, Jung Min Shim, Ian Baines, Edmund G Wee, Philip N Hawkins, Julian D Gillmore, Tomáš Hanke, Mark B Pepys
BACKGROUND: The failure of DNA vaccination in humans, in contrast to its efficacy in some species, is unexplained. Observational and interventional experimental evidence suggests that DNA immunogenicity may be prevented by binding of human serum amyloid P component (SAP). SAP is the single normal DNA binding protein in human plasma. The drug (R)-1-[6-[(R)-2-carboxypyrrolidin-1-yl]-6-oxo-hexanoyl]pyrrolidine-2-carboxylic acid (CPHPC, miridesap), developed for treatment of systemic amyloidosis and Alzheimer's disease, depletes circulating SAP by 95-99%...
2018: PloS One
https://www.readbyqxmd.com/read/29772021/analysis-of-risk-factors-for-mild-cognitive-impairment-based-on-word-list-memory-test-results-and-questionnaire-responses-in-healthy-japanese-individuals-registered-in-an-online-database
#8
Masayo Ogawa, Daichi Sone, Kazushi Maruo, Hiroyuki Shimada, Keisuke Suzuki, Hiroshi Watanabe, Hiroshi Matsuda, Hidehiro Mizusawa
Although the development of effective therapeutic drugs and radical treatment options for dementia and Alzheimer's disease (AD) remains urgent, progress in recent clinical trials of AD drugs has been less than adequate. In order to advance the progress of clinical trials, it is necessary to establish more efficient methods of recruitment. In Japan, there are registration systems stratified by mild cognitive impairment and preclinical and clinical stages of early and advanced stage dementia, but there is no registration system for healthy individuals yet...
2018: PloS One
https://www.readbyqxmd.com/read/29771571/effect-of-weak-combined-static-and-extremely-low-frequency-alternating-magnetic-fields-on-spatial-memory-and-brain-amyloid-%C3%AE-in-two-animal-models-of-alzheimer-s-disease
#9
Natalia V Bobkova, Vadim V Novikov, Natalia I Medvinskaya, Irina Y Aleksandrova, Inna V Nesterova, Eugenii E Fesenko
Subchronic effect of a weak combined magnetic field (MF), produced by superimposing a constant component, 42 µT and an alternating MF of 0.08 µT, which was the sum of two frequencies of 4.38 and 4.88 Hz, was studied in olfactory bulbectomized (OBE) and transgenic Tg (APPswe, PSEN1) mice, which were used as animal models of sporadic and heritable Alzheimer's disease (AD) accordingly. Spatial memory was tested in a Morris water maze on the following day after completion of training trials with the hidden platform removed...
May 17, 2018: Electromagnetic Biology and Medicine
https://www.readbyqxmd.com/read/29765306/microglial-activation-is-modulated-by-captopril-in-vitro-and-in-vivo-studies
#10
Keren Asraf, Nofar Torika, Ron N Apte, Sigal Fleisher-Berkovich
The renin-angiotensin system (RAS) is an important peripheral system involved in homeostasis modulation, with angiotensin II (Ang II) serving as the main effector hormone. The main enzyme involved in Ang II formation is angiotensin-converting enzyme (ACE). ACE inhibitors (ACEIs) such as captopril (Cap) are predominantly used for the management of hypertension. All of the components of the RAS have also been identified in brain. Centrally located hormones such as Ang II can induce glial inflammation. Moreover, in Alzheimer's disease (AD) models, where glial inflammation occurs and is thought to contribute to the propagation of the disease, increased levels of Ang II and ACE have been detected...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29764704/current-understanding-of-neuroinflammation-after-traumatic-brain-injury-and-cell-based-therapeutic-opportunities
#11
REVIEW
Ye Xiong, Asim Mahmood, Michael Chopp
Traumatic brain injury (TBI) remains a major cause of death and disability worldwide. Increasing evidence indicates that TBI is an important risk factor for neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and chronic traumatic encephalopathy. Despite improved supportive and rehabilitative care of TBI patients, unfortunately, all late phase clinical trials in TBI have yet to yield a safe and effective neuroprotective treatment. The disappointing clinical trials may be attributed to variability in treatment approaches and heterogeneity of the population of TBI patients as well as a race against time to prevent or reduce inexorable cell death...
April 24, 2018: Chinese Journal of Traumatology, Zhonghua Chuang Shang za Zhi
https://www.readbyqxmd.com/read/29761891/processed-electroencephalogram-and-evoked-potential-techniques-for-amelioration-of-postoperative-delirium-and-cognitive-dysfunction-following-non-cardiac-and-non-neurosurgical-procedures-in-adults
#12
REVIEW
Yodying Punjasawadwong, Waraporn Chau-In, Malinee Laopaiboon, Sirivimol Punjasawadwong, Pathomporn Pin-On
BACKGROUND: Postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) may complicate a patient's postoperative recovery in several ways. Monitoring of processed electroencephalogram (EEG) or evoked potential (EP) indices may prevent or minimize POD and POCD, probably through optimization of anaesthetic doses. OBJECTIVES: To assess whether the use of processed EEG or auditory evoked potential (AEP) indices (bispectral index (BIS), narcotrend index, cerebral state index, state entropy and response entropy, patient state index, index of consciousness, A-line autoregressive index, and auditory evoked potentials (AEP index)) as guides to anaesthetic delivery can reduce the risk of POD and POCD in non-cardiac surgical or non-neurosurgical adult patients undergoing general anaesthesia compared with standard practice where only clinical signs are used...
May 15, 2018: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/29759072/chat-gene-polymorphism-rs3810950-is-associated-with-the-risk-of-alzheimer-s-disease-in-the-czech-population
#13
Alice Hálová, Jana Janoutová, Laura Ewerlingová, Vladimír Janout, Ondřej Bonczek, Tomáš Zeman, Tereza Gerguri, Vladimir J Balcar, Omar Šerý
BACKGROUND: Cholinergic hypothesis of Alzheimer's disease (AD) is based on the findings that a reduced and/or perturbed cholinergic activity in the central nervous system correlates with cognitive decline in patients with Alzheimer's disease. The hypothesis resulted in the development of centrally-acting agents potentiating cholinergic neurotransmission; these drugs, however, only slowed down the cognitive decline and could not prevent it. Consequently, the perturbation of the central cholinergic signalling has been accepted as a part of the Alzheimer's aetiology but not necessarily the primary cause of the disease...
May 14, 2018: Journal of Biomedical Science
https://www.readbyqxmd.com/read/29757991/a-review-the-bioactivities-and-pharmacological-applications-of-polygonatum-sibiricum-polysaccharides
#14
REVIEW
Xiaowei Cui, Shiyuan Wang, Hui Cao, Hong Guo, Yujuan Li, Fangxue Xu, Mengmeng Zheng, Xiaozhi Xi, Chunchao Han
Traditional Chinese Medicine (TCM) has been widely used in China and is regarded as the most important therapeutic. Polygonatum sibiricum (PS), a natural plant used in traditional Chinese medicine, has various functions associated with a number of its components. There are many compositions in PS including polysaccharides, steroids, anthraquinone, alkaloids, cardiac glycosides, lignin, vitamins, various acids, and so on. Of these, polysaccharides play a significant role in PS-based therapeutics. This article summarizes Polygonatum sibiricum polysaccharides (PSP) have many pharmacological applications and biological activities, such as their antioxidant activity, anti-aging activity, an anti-fatigue effect, immunity enhancement effect, antibacterial effect, anti-inflammatory effect, hypolipidemic and antiatherosclerotic effects, anti-osteoporosis effect, liver protection, treatment of diabetes mellitus (DM), anti-cancer effect, and may help prevent Alzheimer's disease, and so on...
May 14, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29755713/a-mobile-multimedia-reminiscence-therapy-application-to-reduce-behavioral-and-psychological-symptoms-in-persons-with-alzheimer-s
#15
Danish Imtiaz, Arshia Khan, Adriana Seelye
The goal of this project is to develop a novel and innovative mobile solution to address behavioral and psychological symptoms of dementia (BPSD) that occur in individuals with Alzheimer's. BPSD can include agitation, restlessness, aggression, apathy, obsessive-compulsive and repetitive behaviors, hallucinations, delusions, paranoia, and wandering. Alzheimer's currently affects 5.4 million adults in the United States and that number is projected to increase to 14 million by 2050. Almost 90% of all affected with AD experience BPSD, resulting in increased healthcare costs, heavier burden on caregivers, poor patient outcomes, early nursing home placement, long-term hospitalizations, and misuse of medications...
2018: Journal of Healthcare Engineering
https://www.readbyqxmd.com/read/29754747/sexual-dimorphism-in-predisposition-to-alzheimer-s-disease
#16
REVIEW
Daniel W Fisher, David A Bennett, Hongxin Dong
Clinical studies indicate that Alzheimer's disease (AD) disproportionately affects women in both disease prevalence and rate of symptom progression, but the mechanisms underlying this sexual divergence are unknown. Although some have suggested this difference in risk is a reflection of the known differences in longevity between men and women, mounting clinical and preclinical evidence supports women also having intrinsic susceptibilities toward the disease. Although a number of potential risk factors have been hypothesized to mediate these differences, none have been definitively verified...
April 17, 2018: Neurobiology of Aging
https://www.readbyqxmd.com/read/29754175/stem-cell-therapies-for-neurodegenerative-diseases
#17
Kiminobu Sugaya, Manjusha Vaidya
Stem cell therapies have been proposed as a treatment option for neurodegenerative diseases, but the best stem cell source and therapeutic efficacy for neuroregeneration remain uncertain. Embryonic stem cells (ESCs) and neural stem cells (NSCs), which can efficiently generate neural cells, could be good candidates but they pose ethical and practical issues. Not only difficult to find the good source of those cells but also they alway pose immunorejection problem since they may not be an autologous cells. Even if we overcome the immunorejection problem, it has also been reported that transplantation of ESCs develop teratoma...
2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29751013/the-properties-of-amyloid-%C3%AE-fibrils-are-determined-by-their-path-of-formation
#18
Kristoffer Brännström, Tohidul Islam, Anna L Gharibyan, Irina Iakovleva, Lina Nilsson, Cheng Choo Lee, Linda Sandblad, Annelie Pamrén, Anders Olofsson
Fibril formation of the amyloid-β peptide (Aβ) follows a nucleation-dependent polymerization process and is associated with Alzheimer's disease. Several different lengths of Aβ are observed in vivo, but Aβ1-40 and Aβ1-42 are the dominant forms. The fibril architectures of Aβ1-40 and Aβ1-42 differ and Aβ1-42 assemblies are generally considered more pathogenic. We show here that monomeric Aβ1-42 can be cross-templated and incorporated into the ends of Aβ1-40 fibrils, while incorporation of Aβ1-40 monomers into Aβ1-42 fibrils is very poor...
May 8, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29745864/modulation-of-the-expression-of-genes-related-to-the-system-of-amyloid-beta-metabolism-in-the-brain-as-a-novel-mechanism-of-ceftriaxone-neuroprotective-properties
#19
Maria A Tikhonova, Tamara G Amstislavskaya, Victor M Belichenko, Larisa A Fedoseeva, Sergey P Kovalenko, Ekaterina E Pisareva, Alla S Avdeeva, Nataliya G Kolosova, Nikolai D Belyaev, Lyubomir I Aftanas
BACKGROUND: The dominant hypothesis about the pathogenesis of Alzheimer's disease (AD) is the "amyloid cascade" concept and modulating the expression of proteins involved in the metabolism of amyloid-beta (Aβ) is proposed as an effective strategy for the prevention and therapy of AD. Recently, we found that an antibiotic ceftriaxone (CEF), which possesses neuroprotective activity, reduced cognitive deficits and neurodegenerative changes in OXYS rats, a model of sporadic AD...
April 19, 2018: BMC Neuroscience
https://www.readbyqxmd.com/read/29745510/-detection-algorithm-of-amyloid-%C3%AE-protein-deposition-in-magnetic-resonance-image-based-on-pixel-feature-learning-method
#20
Fang Yan, Yongming Li, Xueru Zhu, Jie Wang, Pin Wang, Fan Li, Mingguo Qiu, Jian Qin
Amyloid β-protein (Aβ) deposition is an important prevention and treatment target for Alzheimer's disease (AD), and early detection of Aβ deposition in the brain is the key to early diagnosis of AD. Magnetic resonance imaging (MRI) is the perfect imaging technology for the clinical diagnosis of AD, but it cannot display the plaque deposition directly. In this paper, based on two feature selection modes-filter and wrapper, chain-like agent genetic algorithm (CAGA), principal component analysis (PCA), support vector machine (SVM) and random forest (RF), we designed six kinds of feature learning classification algorithms to detect the information (distribution) of Aβ deposition through magnetic resonance image pixels selection...
June 1, 2017: Sheng Wu Yi Xue Gong Cheng Xue za Zhi, Journal of Biomedical Engineering, Shengwu Yixue Gongchengxue Zazhi
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