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https://www.readbyqxmd.com/read/29779041/the-potential-importance-of-myeloid-derived-suppressor-cells-mdscs-in-the-pathogenesis-of-alzheimer-s-disease
#1
REVIEW
Antero Salminen, Kai Kaarniranta, Anu Kauppinen
The exact cause of Alzheimer's disease (AD) is still unknown, but the deposition of amyloid-β (Aβ) plaques and chronic inflammation indicates that immune disturbances are involved in AD pathogenesis. Recent genetic studies have revealed that many candidate genes are expressed in both microglia and myeloid cells which infiltrate into the AD brains. Invading myeloid cells controls the functions of resident microglia in pathological conditions, such as AD pathology. AD is a neurologic disease with inflammatory component where the immune system is not able to eliminate the perpetrator, while, concurrently, it should prevent neuronal injuries induced by inflammation...
May 19, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29777707/functional-analysis-of-juxta-and-intra-membrane-domains-of-murine-app-by-genome-editing-in-neuro2a-cells
#2
Nanaka Kaneshiro, Ryosuke Imaoka, Masato Komai, Taku Kashiyama, Takashi Sakurai, Takashi Uehara, Nobumasa Takasugi
Amyloid-β precursor protein (APP) correlates with the pathogenesis of certain brain diseases, such as Alzheimer disease (AD). APP is cleaved by several enzymes to produce APP metabolites, including the amyloid beta peptide (Aβ), which accumulates in the brain of AD patients. However, the exact functions of APP metabolites remain elusive. In this study, using genome editing technology, we mutated juxta- and intra-membrane domains of murine APP in the mouse neuroblastoma cell line, Neuro2a. We identified several clones that expressed characteristic patterns of APP metabolites...
May 16, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29775888/therapeutic-impact-of-rhuepo-on-abnormal-platelet-app-bace-1-presenilin-1-adam-10-and-a%C3%AE-expressions-in-chronic-kidney-disease-patients-with-cognitive-dysfunction-like-alzheimer-s-disease-a-pilot-study
#3
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...
May 14, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29775538/discovery-of-potent-and-centrally-active-6-substituted-5-fluoro-1-3-dihydro-oxazine-%C3%AE-secretase-bace1-inhibitors-via-active-conformation-stabilization
#4
Kenji Nakahara, Kouki Fuchino, Kazuo Komano, Naoya Asada, Genta Tadano, Tsuyoshi Hasegawa, Takahiko Yamamoto, Yusuke Sako, Masayoshi Ogawa, Chie Unemura, Motoko Hosono, Hisanori Ito, Gaku Sakaguchi, Shigeru Ando, Shuichi Ohnishi, Yasuto Kido, Tamio Fukushima, Deborah Dhuyvetter, Herman Borghys, Harrie J M Gijsen, Yoshinori Yamano, Yasuyoshi Iso, Ken-Ichi Kusakabe
β-Secretase (BACE1) has an essential role in the production of amyloid β peptides that accumulate in patients with Alzheimer's disease (AD). Thus, inhibition of BACE1 is considered to be a disease-modifying approach for the treatment of AD. Our hit-to-lead efforts led to a cellular potent 1,3-dihydro-oxazine 6, which however inhibited hERG and showed high P-gp efflux. The close analog of 5-fluoro-oxazine 8 reduced P-gp efflux; further introduction of electron withdrawing groups at the 6-position improved potency and also mitigated P-gp efflux and hERG inhibition...
May 18, 2018: Journal of Medicinal 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
#5
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/29774334/a-comparative-study-of-epa-enriched-ethanolamine-plasmalogen-and-epa-enriched-phosphatidylethanolamine-on-a%C3%AE-42-induced-cognitive-deficiency-in-a-rat-model-of-alzheimer-s-disease
#6
Hongxia Che, Qian Li, Tiantian Zhang, Lin Ding, Lingyu Zhang, Haohao Shi, Teruyoshi Yanagita, Changhu Xue, Yaoguang Chang, Yuming Wang
Ethanolamine plasmalogen (pPE), a major phospholipid in neuronal membranes, is specifically reduced in postmortem brains from patients with Alzheimer's disease (AD). The purpose of the present study was to compare the effects of EPA-enriched ethanolamine plasmalogen (EPA-pPE) and EPA-enriched phosphatidylethanolamine (EPA-PE) on cognitive deficiency and illustrate the possible underlying mechanisms. SD rats were divided into four groups including the sham group injected with 0.9% saline and three amyloid-β (Aβ) infusion groups, Aβ42 group, EPA-pPE group and EPA-PE group...
May 18, 2018: Food & Function
https://www.readbyqxmd.com/read/29772895/reversible-assembly-of-a-drug-peptide-into-amyloid-fibrils-a-dynamic-circular-dichroism-study
#7
Frédéric Gobeaux, Frank Wien
The common view on the amyloid fibril formation is that it is a multistep process that involves many oligomeric intermediate species, which leads to a high degree of polymorphism. This view derives from numerous kinetic studies whose vast majority was carried out with amyloid β fragments or other pathological amyloidogenic sequences. Yet, it is not clear whether the mechanisms inferred from these studies are universal and also apply to functional amyloids, in particular to peptide hormones which form reversible amyloid structures...
May 18, 2018: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/29772059/the-orphan-g-protein-coupled-receptor-75-signaling-is-activated-by-the-chemokine-ccl5
#8
Simona Dedoni, Lee A Campbell, Brandon K Harvey, Valeria Avdoshina, Italo Mocchetti
The chemokine CCL5 prevents neuronal cell death mediated both by amyloid β, as well as the human immunodeficiency virus (HIV) viral proteins gp120 and Tat. Because CCL5 binds to CCR5, CCR3 and/or CCR1 receptors, it is unclear which of these receptors plays a role in neuroprotection. Indeed, CCL5 also has neuroprotective activity in cells lacking these receptors. CCL5 may bind to a G protein-coupled receptor 75 (GPR75), which encodes for a 540 amino-acid orphan receptor of the Gqα family. In this study, we have used SH-SY5Y human neuroblastoma cells to characterize whether CCL5 could activate a Gq signaling through GPR75...
May 17, 2018: Journal of Neurochemistry
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/29771495/rapid-growth-of-acetylated-a%C3%AE-16-20-into-macroscopic-crystals
#10
Christian Bortolini, Lasse Hyldgaard Klausen, Søren Vrønning Hoffmann, Nykola C Jones, Daniela Saadeh, Zegao Wang, Tuomas P J Knowles, Mingdong Dong
Aberrant assembly of the amyloid-β (Aβ) is responsible for the development of Alzheimer's disease, but can also be exploited to obtain highly functional biomaterials. The short Aβ fragment, KLVFF (Aβ16-20), is crucial for Aβ assembly and considered to be an Aβ aggregation inhibitor. Here, we show that acetylation of KLVFF turns it into an extremely fast self-assembling molecule, reaching macroscopic (i.e. mm) size in seconds. We show that KLVFF is metastable and that the self-assembly can be directed towards a crystalline or fibrillar phase simply through chemical modification, via acetylation or amidation of the peptide...
May 17, 2018: ACS Nano
https://www.readbyqxmd.com/read/29771464/degradation-of-amyloid-%C3%AE-peptide-by-neprilysin-expressed-from-borna-disease-virus-vector
#11
Madoka Sakai, Sakiho Ueda, Takuji Daito, Megumi Asada-Utsugi, Yumiko Komatsu, Ayae Kinoshita, Takakuni Maki, Akira Kuzuya, Ryosuke Takahashi, Akiko Makino, Keizo Tomonaga
Accumulation of amyloid β (Aβ40 and Aβ42) in the brain is a characteristic of Alzheimer's disease (AD). Because neprilysin (NEP) is a major Aβ-degrading enzyme, NEP delivery in the brain is a promising gene therapy for AD. Borna disease virus (BoDV) vector enables long-term transduction of foreign genes in the central nerve system. Here, we evaluated the proteolytic ability of NEP transduced by the BoDV vector and found that the amounts of Aβ40 and Aβ42 significantly decreased, which suggests that NEP expressed from the BoDV vector is functional to degrade Aβ...
May 17, 2018: Microbiology and Immunology
https://www.readbyqxmd.com/read/29770576/the-extracellular-zn-2-concentration-surrounding-excited-neurons-is-high-enough-to-bind-amyloid-%C3%AE-revealed-by-a-nanowire-transistor
#12
Ankur Anand, Chih-Hung Chi, Subhasree Banerjee, Ming-Yi Chou, Fan-Gang Tseng, Chien-Yuan Pan, Yit-Tsong Chen
The Zn2+ stored in the secretory vesicles of glutamatergic neurons is coreleased with glutamate upon stimulation, resulting in the elevation of extracellular Zn2+ concentration (CZn2+ex). This elevation of CZn2+ex regulates the neurotransmission and facilitates the fibrilization of amyloid-β (Aβ). However, the exact CZn2+ex surrounding neurons under (patho)physiological conditions is not clear and the connection between CZn2+ex and the Aβ fibrilization remains obscure. Here, a silicon nanowire field-effect transistor (SiNW-FET) with the Zn2+ -sensitive fluorophore, FluoZin-3 (FZ-3), to quantify the CZn2+ex in real time is modified...
May 16, 2018: Small
https://www.readbyqxmd.com/read/29765306/microglial-activation-is-modulated-by-captopril-in-vitro-and-in-vivo-studies
#13
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/29764453/ampa-ergic-regulation-of-amyloid-%C3%AE-levels-in-an-alzheimer-s-disease-mouse-model
#14
Jane C Hettinger, Hyo Lee, Guojun Bu, David M Holtzman, John R Cirrito
BACKGROUND: Extracellular aggregation of the amyloid-β (Aβ) peptide into toxic multimers is a key event in Alzheimer's disease (AD) pathogenesis. Aβ aggregation is concentration-dependent, with higher concentrations of Aβ much more likely to form toxic species. The processes that regulate extracellular levels of Aβ therefore stand to directly affect AD pathology onset. Studies from our lab and others have demonstrated that synaptic activity is a critical regulator of Aβ production through both presynaptic and postsynaptic mechanisms...
May 15, 2018: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/29763806/a-review-on-flavonoid-based-scaffolds-as-multi-target-directed-ligands-mtdls-for-alzheimer-s-disease
#15
REVIEW
Leili Jalili-Baleh, Elaheh Babaei, Shahin Abdpour, Syed Nasir Abbas Bukhari, Alireza Foroumadi, Ali Ramazani, Mohammad Sharifzadeh, Mohammad Abdollahi, Mehdi Khoobi
Alzheimer's disease (AD), the most common form of dementia, is a multifactorial neurodegenerative disease. The target enzymes inhibition including cholinesterase, beta-secretase, monoamine oxidase and inhibition of amyloid-β aggregation as well as oxidative stress and metal chelation play an important role in the pathogenesis of AD. Chroman-4-one scaffold with benzo-γ-pyrone network is a privileged structure in organic synthesis and drug design. A large number of research has been carried out on modified naturally occurring chromanone scaffolds and/or synthesized new analogues, to obtain effective drugs for AD management...
May 7, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29760290/-senile-dementia-of-the-neurofibrillary-tangle-type-sd-nft
#16
Masahito Yamada
A subset of older individuals with dementia have neurofibrillary tangles (NFTs) in the medial temporal lobe and show absence of amyloid β-protein (Aβ) deposition in the brain. In 1996, the author's group reported senile dementia of the NFT type (SD-NFT) as a disease entity characterized by these pathological features as well as late-onset dementia in older subjects. In 2014, it was proposed that this pathological condition, irrespective of the presence of cognitive impairment, should be referred to as primary age-related tauopathy (PART)...
May 2018: Brain and Nerve, Shinkei Kenkyū No Shinpo
https://www.readbyqxmd.com/read/29760289/-neurocognitive-disorders-other-than-alzheimer-disease-vascular-dementia
#17
Mari Yoshida
Vascular dementia involves several mechanism of pathogenesis. Cerebral small vessel diseases play a central role in vascular dementia, including sporadic cerebral small vessel diseases, cerebral autosomal-dominant or autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL or CARASIL), cerebral amyloid angiopathy, and amyloid β-related angiitis. Although these diseases have different pathomechanisms, chronic white matter hypoperfusion contributes to development of neuronal dysfunction as a common pathway in vascular dementia...
May 2018: Brain and Nerve, Shinkei Kenkyū No Shinpo
https://www.readbyqxmd.com/read/29760078/chaperone-ampylation-modulates-aggregation-and-toxicity-of-neurodegenerative-disease-associated-polypeptides
#18
Matthias C Truttmann, David Pincus, Hidde L Ploegh
Proteostasis is critical to maintain organismal viability, a process counteracted by aging-dependent protein aggregation. Chaperones of the heat shock protein (HSP) family help control proteostasis by reducing the burden of unfolded proteins. They also oversee the formation of protein aggregates. Here, we explore how AMPylation, a posttranslational protein modification that has emerged as a powerful modulator of HSP70 activity, influences the dynamics of protein aggregation. We find that adjustments of cellular AMPylation levels in Caenorhabditis elegans directly affect aggregation properties and associated toxicity of amyloid-β (Aβ), of a polyglutamine (polyQ)-extended polypeptide, and of α-synuclein (α-syn)...
May 14, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29758940/self-reported-physical-activity-is-associated-with-tau-burden-measured-by-positron-emission-tomography
#19
Belinda M Brown, Stephanie R Rainey-Smith, Vincent Dore, Jeremiah J Peiffer, Samantha C Burnham, Simon M Laws, Kevin Taddei, David Ames, Colin L Masters, Christopher C Rowe, Ralph N Martins, Victor L Villemagne
Numerous animal studies have reported exercise reduces the accumulation of Alzheimer's disease pathology, including amyloid-β (Aβ) and tau. Furthermore, we previously reported a relationship between higher levels of physical activity (PA) and lower brain Aβ burden in a human population. The recent advent of tau positron emission tomography (PET) tracers enables us to extend our investigations into the evaluation of the relationship between PA and brain tau burden. Utilizing data from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study, we have examined the cross-sectional relationship between habitual PA and PET-quantified tau burden...
May 11, 2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29755842/lipopolysaccharide-endotoxemia-induces-amyloid-%C3%AE-and-p-tau-formation-in-the-rat-brain
#20
Li-Ming Wang, Qi Wu, Ryan A Kirk, Kevin P Horn, Ahmed H Ebada Salem, John M Hoffman, Jeffrey T Yap, Joshua A Sonnen, Rheal A Towner, Fernando A Bozza, Rosana S Rodrigues, Kathryn A Morton
Amyloid beta (Aβ) plaques are not specific to Alzheimer's disease and occur with aging and neurodegenerative disorders. Soluble brain Aβ may be neuroprotective and increases in response to neuroinflammation. Sepsis is associated with neurocognitive compromise. The objective was to determine, in a rat endotoxemia model of sepsis, whether neuroinflammation and soluble Aβ production are associated with Aβ plaque and hyperphosphorylated tau deposition in the brain. Male Sprague Dawley rats received a single intraperitoneal injection of 10 mg/kg of lipopolysaccharide endotoxin (LPS)...
2018: American Journal of Nuclear Medicine and Molecular Imaging
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