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https://www.readbyqxmd.com/read/29350764/the-protective-effect-of-antarctic-krill-oil-on-cognitive-function-by-inhibiting-oxidative-stress-in-the-brain-of-senescence-accelerated-prone-mouse-strain-8-samp8-mice
#1
Qian Li, Fengjuan Wu, Min Wen, Teruyoshi Yanagita, Changhu Xue, Tiantian Zhang, Yuming Wang
Alzheimer's disease (AD) is a common neurodegenerative disorder, and oxidative stress plays a vital role in its progression. Antarctic krill oil (AKO) is rich in polyunsaturated fatty acids, which has various biological activities, such as improving insulin sensitivity, alleviating inflammation and ameliorating oxidative stress. In this study, the protective effect of AKO against AD were investigated in senescence-accelerated prone mouse strain 8 (SAMP8) mice. Results showed that treatment with AKO could effectively ameliorate learning and memory deficits and ease the anxiety in SAMP8 mice by Morris water maze, Barnes maze test and open-field test...
January 19, 2018: Journal of Food Science
https://www.readbyqxmd.com/read/29350601/brain-tissue-a%C3%AE-42-levels-are-linked-to-shunt-response-in-idiopathic-normal-pressure-hydrocephalus
#2
Sami Abu Hamdeh, Johan Virhammar, Dag Sehlin, Irina Alafuzoff, Kristina Giuliana Cesarini, Niklas Marklund
OBJECTIVE The authors conducted a study to test if the cortical brain tissue levels of soluble amyloid beta (Aβ) reflect the propensity of cortical Aβ aggregate formation and may be an additional factor predicting surgical outcome following idiopathic normal pressure hydrocephalus (iNPH) treatment. METHODS Highly selective ELISAs (enzyme-linked immunosorbent assays) were used to quantify soluble Aβ40, Aβ42, and neurotoxic Aβ oligomers/protofibrils, associated with Aβ aggregation, in cortical biopsy samples obtained in patients with iNPH (n = 20), sampled during ventriculoperitoneal (VP) shunt surgery...
January 19, 2018: Journal of Neurosurgery
https://www.readbyqxmd.com/read/29349888/distal-amyloid-%C3%AE-protein-fragments-template-amyloid-assembly
#3
Thanh D Do, Smriti Sangwan, Natália E C de Almeida, Alexandre I Ilitchev, Maxwell Giammona, Michael R Sawaya, Steven K Buratto, David S Eisenberg, Michael T Bowers
Amyloid formation is associated with devastating diseases such as Alzheimer's, Parkinson's and Type-2 diabetes. The large amyloid deposits found in patients suffering from these diseases have remained difficult to probe by structural means. Recent NMR models also predict heterotypic interactions from distinct peptide fragments but limited evidence of heterotypic packed sheets is observed in solution. Here we characterize two segments of the protein amyloid β (Aβ) known to form fibrils in Alzheimer's disease patients...
January 19, 2018: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/29349578/in-situ-tissue-labeling-of-cerebral-amyloid-using-hiv-related-tat-peptide
#4
E Maderna, L Colombo, A Cagnotto, G Di Fede, A Indaco, F Tagliavini, M Salmona, G Giaccone
Delivering peptide-based drugs to the brain is a major challenge because of the existence of the blood-brain barrier (BBB). To overcome this problem, cell-penetrating peptides derived from proteins that are able to cross biological membranes have been used as cell-permeable and brain-penetrant compounds. An example is the transactivator of transcription protein transduction domain (Tat) of the human immunodeficiency virus. The basic domain of Tat is formed of arginine and lysine amino acid residues. Tat has been used as brain-penetrant carrier also in therapies for Alzheimer disease (AD), the most common form of dementia characterized by extracellular cerebral deposits of amyloid made up of Aβ peptide...
January 19, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29348604/cromolyn-reduces-levels-of-the-alzheimer-s-disease-associated-amyloid-%C3%AE-protein-by-promoting-microglial-phagocytosis
#5
Can Zhang, Ana Griciuc, Eloise Hudry, Yu Wan, Luisa Quinti, Joseph Ward, Angela M Forte, Xunuo Shen, ChongZhao Ran, David R Elmaleh, Rudolph E Tanzi
Amyloid-beta protein (Aβ) deposition is a pathological hallmark of Alzheimer's disease (AD). Aβ deposition triggers both pro-neuroinflammatory microglial activation and neurofibrillary tangle formation. Cromolyn sodium is an asthma therapeutic agent previously shown to reduce Aβ levels in transgenic AD mouse brains after one-week of treatment. Here, we further explored these effects as well as the mechanism of action of cromolyn, alone, and in combination with ibuprofen in APPSwedish-expressing Tg2576 mice...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29348391/effects-of-senescence-and-angiotensin-ii-on-expression-and-processing-of-amyloid-precursor-protein-in-human-cerebral-microvascular-endothelial-cells
#6
Ruohan Sun, Tongrong He, Yujun Pan, Zvonimir S Katusic
The present study was designed to determine the effects of senescence and angiotensin II (Ang II) on expression and processing of amyloid precursor protein (APP) in human brain microvascular endothelial cells (BMECs). Senescence caused a decrease in APP expression thereby resulting in reduced secretion of soluble APPα (sAPPα). In contrast, β-site APP cleaving enzyme (BACE1) expression and production of amyloid β (Aβ)40 were increased in senescent endothelium. Importantly, in senescent human BMECs, treatment with BACE1 inhibitor IV inhibited Aβ generation and increased sAPPα production by enhancing a disintegrin and metalloprotease (ADAM)10 expression...
January 15, 2018: Aging
https://www.readbyqxmd.com/read/29348375/-suspected-non-alzheimer-s-disease-pathophysiology-snap-and-its-pathological-backgrounds-in-the-diagnosis-of-preclinical-and-clinical-alzheimer-s-disease
#7
Masahito Yamada
Suspected non-Alzheimer's disease pathophysiology (SNAP) is a biomarker-based condition that is found in individuals with normal levels of amyloid-β protein (Aβ) markers (A-) and abnormal levels of markers of neurodegeneration or neuronal injury (N+). SNAP is found in 20-26% of cognitively normal (CN) individuals aged 65 years or older and 17-35% of individuals with mild cognitive impairment (MCI). Similarly, 7-39% of patients with clinically probable Alzheimer's disease (AD) dementia are negative for Aβ...
January 2018: Brain and Nerve, Shinkei Kenkyū No Shinpo
https://www.readbyqxmd.com/read/29345897/design-synthesis-and-biological-evaluation-of-1-benzylamino-2-hydroxyalkyl-derivatives-as-new-potential-disease-modifying-multifunctional-anti-alzheimer-s-agents
#8
Dawid Panek, Anna Więckowska, Jakub Jończyk, Justyna Godyń, Marek W Bajda, Tomasz Wichur, Anna Pasieka, Damijan Knez, Anja Pislar, Jan Korabecny, Ondrej Soukup, Vendula Sepsova, Raimon Sabaté, Janko Kos, Stanislav Gobec, Barbara Malawska
The multitarget approach is a promising paradigm in drug discovery, potentially leading to new treatment options for complex disorders, such as Alzheimer's disease. Herein, we present the discovery of a unique series of 1-benzylamino-2-hydroxyalkyl derivatives combining inhibitory activity against butyrylcholinesterase, β-secretase, β-amyloid and tau protein aggregation, all related to mechanisms which underpin Alzheimer's disease. Notably, diphenylpropylamine derivative 10 showed balanced activity against both disease-modifying targets - inhibition of β-secretase (IC50 hBACE-1 = 41...
January 18, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29345424/a-fluorescence-based-sensor-assay-that-monitors-general-protein-aggregation-in-human-cells
#9
Marisa Pereira, Diogo Tomé, Ana S Domingues, Ana S Varanda, Cristiana Paulo, Manuel A S Santos, Ana R Soares
Protein conformational disorders are characterized by disruption of protein folding and toxic accumulation of protein aggregates. Here we describe a sensitive and simple method to follow and monitor general protein aggregation in human cells. Heat shock protein 27 (HSP27) is an oligomeric small heat shock protein that binds and keeps unfolded proteins in a folding competent state. This high specificity of HSP27 for aggregated proteins can be explored to monitor aggregation in living cells by fusing it to a fluorescent protein as Green Fluorescent Protein (GFP)...
January 18, 2018: Biotechnology Journal
https://www.readbyqxmd.com/read/29345339/the-role-of-cdk5-mediated-drp1-phosphorylation-in-a%C3%AE-1-42-induced-mitochondrial-fission-and-neuronal-apoptosis
#10
Miao-Yu Guo, Lei Shang, Yang-Yang Hu, Li-Ping Jiang, Yu-Ying Wan, Qin-Qin Zhou, Kun Zhang, Hong-Fei Liao, Jing-Lin Yi, Xiao-Jian Han
Alzheimer's disease, one of the most common neurodegenerative diseases, is pathologically characterized by Amyloid beta containing plaques and neurofibrillary tangles. Amyloid beta (Aβ) induces neuronal apoptosis through the intracellular Ca2+ increase, subsequent hyperactivation of cyclin-dependent kinase 5 (Cdk5) and mitochondrial abnormality. Recently, Cdk5 was identified as an upstream regulator of mitochondrial fission during neuronal apoptosis, but the underlying mechanism remains unclear. Here, in vitro phosphorylation assays showed that Cdk5 could phosphorylate the recombinant Drp1 at Serine 579...
January 18, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29345054/isoflurane-anesthesia-in-aged-mice-and-effects-of-a1-adenosine-receptors-on-cognitive-impairment
#11
Chun-Long Zuo, Chun-Man Wang, Jin Liu, Ting Shen, Jiang-Ping Zhou, Xin-Rui Hao, Yi-Zhao Pan, Hua-Cheng Liu, Qing-Quan Lian, Han Lin
AIMS: Isoflurane may not only accelerate the process of Alzheimer's disease (AD), but increase the risk of incidence of postoperative cognitive dysfunction (POCD). However, the underlying mechanisms remain unknown. This study was designed to investigate whether isoflurane contributed to the POCD occurrence through A1 adenosine receptor (A1AR) in aged mice. METHODS: We assessed cognitive function of mice with Morris water maze (MWM) and then measured expression level of two AD biomarkers (P-tau and Aβ) and a subtype of the NMDA receptor (NR2B) in aged wild-type (WT) and homozygous A1 adenosine receptor (A1AR) knockout (KO) mice at baseline and after they were exposed to isoflurane (1...
January 17, 2018: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/29341888/protection-against-the-neurotoxic-effects-of-%C3%AE-amyloid-peptide-on-cultured-neuronal-cells-by-lovastatin-involves-elevated-expression-of-%C3%AE-7-nicotinic-acetylcholine-receptors-and-activating-phosphorylation-of-protein-kinases
#12
Liang Zhao, Yan Xiao, Jin Xiu, Long-Chun Tan, Zhi-Zhong Guan
The treatment of neurodegenerative diseases with statins has drawn increasing attention, but the related molecular mechanisms remain elusive. To examine the pleiotropic cholesterol-independent effects of statins in connection with the treatment of Alzheimer disease, we probed the influence of lovastatin on the metabolism of amyloid precursor protein (APP) , expression of nicotinic acetylcholine receptors (nAChRs), and activity of mitogen-activated protein kinase in primary cultured neurons and SH-SY5Y cells over-expressing human APP670/671...
January 13, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29341269/characterization-of-a-3xtg-ad-mouse-model-of-alzheimer-s-disease-with-the-senescence-accelerated-mouse-prone-8-samp8-background
#13
Jessica Virgili, Meryem Lebbadi, Cyntia Tremblay, Isabelle St-Amour, Caroline Pierrisnard, Audrey Faucher-Genest, Vincent Emond, Carl Julien, Frédéric Calon
No model fully recapitulates the neuropathology of Alzheimer's disease (AD). Although the triple-transgenic mouse model of AD (3xTg-AD) expresses Aβ plaques and tau-laden neurofibrillary tangles, as well as synaptic and behavioral deficits, it does not display frank neuronal loss. Since old age is the most important risk factor in AD, senescence-related interactions might be lacking to truly establish an AD-like environment. To investigate this hypothesis, we bred the 3xTg-AD mouse with the senescence-accelerated mouse prone 8 (SAMP8), a model of accelerated aging...
January 17, 2018: Synapse
https://www.readbyqxmd.com/read/29339255/design-synthesis-and-biological-evaluation-of-lx2343-derivatives-as-neuroprotective-agents-for-the-treatment-of-alzheimer-s-disease
#14
Guanglong Sun, Junwei Wang, Xiaodan Guo, Min Lei, Yinan Zhang, Xiachang Wang, Xu Shen, Lihong Hu
A series of LX2343 derivatives were designed, synthesized and evaluated as neuroprotective agents for Alzheimer's disease (AD) in vitro. Most of the compounds displayed potent neuroprotective activities. Especially for compound A6, exhibited a remarkable EC50 value of 0.22 μM. Further investigation demonstrated that compound A6 can significantly reduce Aβ production and increase Aβ clearance, and alleviate Tau hyperphosphorylation. Most importantly, compound A6 could ameliorate learning and memory impairments in APP/PS1 transgenic mice...
January 2, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29339171/dna-methylation-level-of-the-neprilysin-promoter-in-alzheimer-s-disease-brains
#15
Kenichi Nagata, Tatsuo Mano, Shigeo Murayama, Takaomi C Saido, Atsushi Iwata
Neprilysin (NEP), a membrane-bound metalloprotease, has been shown to play an essential role in the clearance of amyloid beta (Aβ) peptides. Previous studies have reported that NEP expression is downregulated in the normal aging brain as well as in the Alzheimer's disease (AD) brain, providing evidence that the downregulation of NEP expression contributes to the age-dependent deposition of Aβ-containing plaques, a pathological hallmark of AD. However, the mechanisms underlying the downregulation remain unclear...
January 12, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29339105/effects-of-thymol-on-amyloid-%C3%AE-induced-impairments-in-hippocampal-synaptic-plasticity-in-rats-fed-a-high-fat-diet
#16
Masoumeh Asadbegi, Alireza Komaki, Iraj Salehi, Parichehreh Yaghmaei, Azadeh Ebrahim-Habibi, Siamak Shahidi, Abdolrahman Sarihi, Sara Soleimani Asl, Zoleikha Golipoor
Obesity and a high-fat diet (HFD) are known to increase the incidence of Alzheimer's disease (AD). Oxidative stress, a major risk factor for AD, is increased with HFD consumption. Thymol (Thy) has antioxidant properties. Therefore, in the present study, we examined the protective and therapeutic effects of Thy on amyloid-β (Aβ)-induced impairments in the hippocampal synaptic plasticity of HFD-fed rats. In this study, 72 adult male Wistar rats were randomly assigned to 9 groups (n = 8 rats/group): Group 1 (control; standard diet); Group 2: Control + phosphate-buffered saline (PBS) + Oil (Thy vehicle); Group 3 (HFD + PBS); Group 4: (HFD + Aβ); Group 5: Control + PBS + Thy; Group 6: (HFD + Aβ + Oil); Group 7: Control + Aβ + Thy; Group 8: HFD + PBS + Thy; Group 9: (HFD + Aβ + Thy)...
January 12, 2018: Brain Research Bulletin
https://www.readbyqxmd.com/read/29338754/molecular-and-functional-signatures-in-a-novel-alzheimer-s-disease-mouse-model-assessed-by-quantitative-proteomics
#17
Dong Kyu Kim, Joonho Park, Dohyun Han, Jinhee Yang, Ahbin Kim, Jongmin Woo, Youngsoo Kim, Inhee Mook-Jung
BACKGROUND: Alzheimer's disease (AD), the most common neurodegenerative disorder, is characterized by the deposition of extracellular amyloid plaques and intracellular neurofibrillary tangles. To understand the pathological mechanisms underlying AD, developing animal models that completely encompass the main features of AD pathologies is indispensable. Although mouse models that display pathological hallmarks of AD (amyloid plaques, neurofibrillary tangles, or both) have been developed and investigated, a systematic approach for understanding the molecular characteristics of AD mouse models is lacking...
January 16, 2018: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/29338255/to-be-fibrils-or-to-be-nanofilms-oligomers-are-building-blocks-for-fibrils-and-nanofilms-formation-of-fragments-of-a%C3%AE-peptide
#18
Olga Michailovna Selivanova, Alexey Konstantinovich Surin, Yuriy Ryzhykau, Anna Vladimirovna Glyakina, Mariya Yu Suvorina, Alexander Kuklin, Vadim Rogachevsky, Oxana Valerianovna Galzitskaya
To identify the key stages in the amyloid fibril formation we studied the aggregation of amyloidogenic fragments of Aβ peptide: Aβ(16-25), Aβ(31-40), and Aβ(33-42), using the methods of electron microscopy, ThT fluorescence, X-ray analysis, mass spectrometry, and structural modeling. We have found that the fragments Aβ(31-40) and Aβ(33-42) form amyloid fibrils in the shape of bundles and ribbons, while Aβ(16-25) fragment forms only nanofilms. We are the first who performed 2D reconstruction of amyloid fibrils by the Markham rotation technique on electron micrographs of negatively stained fragments of Aβ peptide...
January 16, 2018: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/29337241/differential-effects-of-alzheimer-s-disease-a%C3%AE-40-and-42-on-endocytosis-and-intraneuronal-trafficking
#19
Rajesh S Omtri, Kevin Thompson, Xiojia Tang, Chaitanya C Gali, Ute Panzenboeck, Michael W Davidson, Krishna R Kalari, Karunya K Kadimalla
Anomalous neuronal accumulation of Aβ peptides was shown to affect synaptic transmission and contribute to neurodegeneration in Alzheimer's disease (AD) brain. Neuronal cells internalize amyloid beta (Aβ) peptides from the brain extracellular space even under normal physiological conditions, and these endocytotic pathways go awry during AD progression. We hypothesized that exposure to toxic Aβ species accumulating in AD brain contribute to perturbations in neuronal endocytosis. We have shown substantial down-regulation of KEGG endocytotic pathway genes in AD patient brain regions that accumulate Aβ compared to those in non-demented individuals...
January 11, 2018: Neuroscience
https://www.readbyqxmd.com/read/29337053/oral-ingestion-of-plasmalogens-can-attenuate-the-lps-induced-memory-loss-and-microglial-activation
#20
Md Shamim Hossain, Ayako Tajima, Satoshi Kotoura, Toshihiko Katafuchi
Plasmalogens (Pls) are the special phospholipids which were reported to be reduced in brain and blood samples of Alzheimer's disease (AD) patients, suggested a possibility that an oral ingestion of Pls may prevent the disease progression. Interestingly, the clinical study showed that the daily oral ingestion of Pls among the mild AD patients improved cognition. However, it is unknown of whether the oral ingestion of Pls inhibits the AD like changes in brain e.g., glial activation and accumulation of amyloid beta (Aβ) proteins...
January 11, 2018: Biochemical and Biophysical Research Communications
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