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https://www.readbyqxmd.com/read/29331684/reprogramming-neurodegeneration-in-the-big-data-era
#1
REVIEW
Lujia Zhou, Patrik Verstreken
Recent genome-wide association studies (GWAS) have identified numerous genetic risk variants for late-onset Alzheimer's disease (AD) and Parkinson's disease (PD). However, deciphering the functional consequences of GWAS data is challenging due to a lack of reliable model systems to study the genetic variants that are often of low penetrance and non-coding identities. Pluripotent stem cell (PSC) technologies offer unprecedented opportunities for molecular phenotyping of GWAS variants in human neurons and microglia...
January 10, 2018: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/29324907/correction-ank1-is-up-regulated-in-laser-captured-microglia-in-alzheimer-s-brain-the-importance-of-addressing-cellular-heterogeneity
#2
Diego Mastroeni, Shobana Sekar, Jennifer Nolz, Elaine Delvaux, Katie Lunnon, Jonathan Mill, Winnie S Liang, Paul D Coleman
[This corrects the article DOI: 10.1371/journal.pone.0177814.].
2018: PloS One
https://www.readbyqxmd.com/read/29321225/humanized-trem2-mice-reveal-microglia-intrinsic-and-extrinsic-effects-of-r47h-polymorphism
#3
Wilbur M Song, Satoru Joshita, Yingyue Zhou, Tyler K Ulland, Susan Gilfillan, Marco Colonna
Alzheimer's disease (AD) is a neurodegenerative disease that causes late-onset dementia. The R47H variant of the microglial receptor TREM2 triples AD risk in genome-wide association studies. In mouse AD models, TREM2-deficient microglia fail to proliferate and cluster around the amyloid-β plaques characteristic of AD. In vitro, the common variant (CV) of TREM2 binds anionic lipids, whereas R47H mutation impairs binding. However, in vivo, the identity of TREM2 ligands and effect of the R47H variant remain unknown...
January 10, 2018: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29319809/increased-microglial-csf1r-expression-in-the-siv-macaque-model-of-hiv-cns-disease
#4
Audrey C Knight, Samuel A Brill, Suzanne E Queen, Patrick M Tarwater, Joseph L Mankowski
Chronic microglial activation and associated neuroinflammation are key factors in neurodegenerative diseases including HIV-associated neurocognitive disorders. Colony stimulating factor 1 receptor (CSF1R)-mediated signaling is constitutive in cells of the myeloid lineage, including microglia, promoting cell survival, proliferation, and differentiation. In amyotrophic lateral sclerosis and Alzheimers disease, CSF1R is upregulated. Inhibiting CSF1R signaling in animal models of these diseases improved disease outcomes...
January 8, 2018: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/29310421/assessment-of-change-in-glucose-metabolism-in-white-matter-of-amyloid-positive-patients-with-alzheimer-disease-using-f-18-fdg-pet
#5
Young Jin Jeong, Hyun Jin Yoon, Do-Young Kang
In Alzheimer disease (AD), neuroinflammation is an important process related to the deposition of beta-amyloid plaques and the activation of microglia. The inflammatory process can occur in both the gray matter and the white matter. We evaluated glucose metabolism of the white matter in AD patients and compared the value with cognitive parameters of the patients.Eighteen AD patients and 18 healthy subjects underwent F-18 fluorodeoxyglucose (FDG) and F-18 florbetaben positron emission tomography (PET). After segmentation of the white matter in both PET images, the specific binding ratio (SBR) of the global and regional cerebral white matter was checked...
December 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29305855/microglia-derived-extracellular-vesicles-in-alzheimer-s-disease-a-double-edged-sword
#6
REVIEW
Teresa Trotta, Maria Antonietta Panaro, Antonia Cianciulli, Giorgio Mori, Adriana Di Benedetto, Chiara Porro
Extracellular vesicles (EVs), based on their origin or size, can be classified as apoptotic bodies, microvesicles (MVs)/microparticles (MPs), and exosomes. EVs are one of the new emerging modes of communication between cells that are providing new insights into the pathophysiology of several diseases. EVs released from activated or apoptotic cells contain specific proteins (signaling molecules, receptors, integrins, cytokines), bioactive lipids, nucleic acids (mRNA, miRNA, small non coding RNAs, DNA) from their progenitor cells...
January 3, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29305438/asymmetric-tdp-pathology-in-primary-progressive-aphasia-with-right-hemisphere-language-dominance
#7
Garam Kim, Shahrooz Vahedi, Tamar Gefen, Sandra Weintraub, Eileen H Bigio, Marek-Marsel Mesulam, Changiz Geula
OBJECTIVE: To quantitatively examine the regional densities and hemispheric distribution of the 43-kDa transactive response DNA-binding protein (TDP-43) inclusions, neurons, and activated microglia in a left-handed patient with right hemisphere language dominance and logopenic-variant primary progressive aphasia (PPA). METHODS: Phosphorylated TDP-43 inclusions, neurons, and activated microglia were visualized with immunohistochemical and histologic methods. Markers were quantified bilaterally with unbiased stereology in language- and memory-related cortical regions...
January 5, 2018: Neurology
https://www.readbyqxmd.com/read/29301548/inhibition-of-cyclin-dependent-kinase-5-affects-early-neuroinflammatory-signalling-in-murine-model-of-amyloid-beta-toxicity
#8
Anna Wilkaniec, Magdalena Gąssowska-Dobrowolska, Marcin Strawski, Agata Adamczyk, Grzegorz A Czapski
BACKGROUND: Cyclin-dependent kinase 5 (Cdk5) belongs to the family of proline-directed serine/threonine kinases and plays a critical role in neuronal differentiation, migration, synaptogenesis, plasticity, neurotransmission and apoptosis. The deregulation of Cdk5 activity was observed in post mortem analysis of brain tissue of Alzheimer's disease (AD) patients, suggesting the involvement of Cdk5 in the pathomechanism of this neurodegenerative disease. However, our recent study demonstrated the important function of Cdk5 in regulating inflammatory reaction...
January 4, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29300354/modulation-of-inducible-nitric-oxide-synthase-expression-in-lps-stimulated-bv-2-microglia-by-prenylated-chalcones-from-cullen-corylifolium-l-medik-through-inhibition-of-i-%C3%AE%C2%BAb%C3%AE-degradation
#9
Do Hee Kim, Hua Li, Yeong Eun Han, Ji Hye Jeong, Hwa Jin Lee, Jae-Ha Ryu
The overproduction of nitric oxide (NO) and prostaglandin E₂ (PGE₂) by microglia may cause neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease. From the activity-guided purification of Cullen corylifolium (L.) Medik. (syn. Psoralea corylifolia L.), three prenylated chalcones were identified: isobavachalcone (1), bavachromene (2), and kanzonol B (3). These prenylated chalcones showed concentration-dependent inhibitory effects on NO and PGE₂ production in lipopolysaccharide (LPS)-activated microglia...
January 4, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29297157/astroglial-responses-to-amyloid-beta-progression-in-a-mouse-model-of-alzheimer-s-disease
#10
Malin Olsen, Ximena Aguilar, Dag Sehlin, Xiaotian T Fang, Gunnar Antoni, Anna Erlandsson, Stina Syvänen
PURPOSE: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by amyloid-beta (Aβ) deposition, hyperphosphorylation of tau, and neuroinflammation. Astrocytes, the most abundant glial cell type in the nervous system, respond to neurodegenerative disorders through astrogliosis, i.e., converting to a reactive inflammatory state. The aim of this study was to investigate how in vivo quantification of astrogliosis using positron emission tomography (PET) radioligand deuterium-L-[11C]deprenyl ([11C]DED), binding to enzyme monoamine oxidase-B (MAO-B) which is overexpressed in reactive astrocytes during AD, corresponds to expression of glial fibrillary acidic protein (GFAP) and vimentin, i...
January 2, 2018: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/29295920/migration-based-selections-of-antibodies-that-convert-bone-marrow-into-trafficking-microglia-like-cells-that-reduce-brain-amyloid-%C3%AE
#11
Kyung Ho Han, Britni M Arlian, Matthew S Macauley, James C Paulson, Richard A Lerner
One goal of regenerative medicine is to repair damaged tissue. This requires not only generating new cells of the proper phenotype, but also selecting for those that properly integrate into sites of injury. In our laboratory we are using a cell-migration-based in vivo selection system to generate antibodies that induce cells to both differentiate and selectively localize to different tissues. Here we describe an antibody that induces bone marrow stem cells to differentiate into microglia-like cells that traffic to the brain where they organize into typical networks...
January 2, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29286084/petasites-japonicus-bakkenolide-b-inhibits-lipopolysaccharide%C3%A2-induced-pro%C3%A2-inflammatory-cytokines-via-ampk-nrf2-induction-in-microglia
#12
Sun Young Park, Min Hyun Choi, Geuntae Park, Young-Whan Choi
Abnormal neuroinflammatory responses have diverse roles in neuronal death, oxidative stress and neurodegenerative diseases, such as Alzheimer's and Parkinson's disease. Microglia regulate these responses via molecular signaling cascades that involve inflammatory cytokines and complement proteins. Bakkenolide B from Petasites japonicus exhibits significant anti‑inflammatory and anti‑allergic bioactivities. The present study investigated the anti‑neuroinflammatory effects and underlying molecular mechanisms of bakkenolide B on the lipopolysaccharide (LPS)‑mediated neuroinflammatory response in microglia...
December 28, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29281977/n-n-disubstituted-azines-attenuate-lps-mediated-neuroinflammation-in-microglia-and-neuronal-apoptosis-via-inhibiting-mapk-signaling-pathways
#13
Lalita Subedi, Oh Wook Kwon, Chaeho Pak, Goeun Lee, Kangwoo Lee, Hakwon Kim, Sun Yeou Kim
BACKGROUND: Activated microglia interact with astrocytes and neuronal cells to induce neuroinflammation, which can contribute to the pathogenesis and progression of Alzheimer's and Parkinson's disease. To identify the most effective anti-neuroinflammatory agent, we designed and synthesized a family of 13 new azine derivatives and investigated their anti-neuroinflammatory activities in LPS-activated BV-2 microglial cells. RESULTS: Out of 13 derivatives, compound 3 [4,4'-(1E,1'E,3E,3'E)-3,3'-(hydrazine-1,2-diylidene) bis-(prop-1-ene-1-yl-3-ylidene) bis-(2-methoxyphenol)] exhibited excellent anti-neuroinflammatory activities (IC50 = 12...
December 28, 2017: BMC Neuroscience
https://www.readbyqxmd.com/read/29278889/erythromyeloid-derived-trem2-a-major-determinant-of-alzheimer-s-disease-pathology-in-down-syndrome
#14
Ruma Raha-Chowdhury, James W Henderson, Animesh Alexander Raha, Simon R W Stott, Romina Vuono, Simona Foscarin, Liam Wilson, Tiina Annus, Robert Fincham, Kieren Allinson, Vinod Devalia, Robert P Friedland, Anthony Holland, Shahid H Zaman
BACKGROUND: Down syndrome (DS; trisomy 21) individuals have a spectrum of hematopoietic and neuronal dysfunctions, and by the time they reach the age of 40 years, almost all develop Alzheimer's disease (AD) neuropathology which includes senile plaques and neurofibrillary tangles. Inflammation and innate immunity are key players in AD and DS. Triggering receptor expressed in myeloid cells-2 (TREM2) variants have been identified as risk factors for AD and other neurodegenerative diseases...
December 16, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29276489/multi-protection-of-dl0410-in-ameliorating-cognitive-defects-in-d-galactose-induced-aging-mice
#15
Wenwen Lian, Hao Jia, Lvjie Xu, Wei Zhou, De Kang, Ailin Liu, Guanhua Du
D-galactose has been reported to accelerate senescence in rodents, accompanied by a decline in learning and memory. We used a model of D-galactose-induced amnesia for the efficacy evaluation and pharmacologic studies of active compounds against Alzheimer's disease (AD). DL0410 is a potent inhibitor against acetylcholinesterase (AChE) and, in the present study, the effect of DL0410 was evaluated in this model. We found that DL0410 could significantly improve the learning and memory of D-galactose induced aging mice in a series of behavioral tests: novel-object recognition test, nest-building test, Morris water maze test and step-through test...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29275160/role-of-the-peripheral-innate-immune-system-in-the-development-of-alzheimer-s-disease
#16
REVIEW
Aurélie Le Page, Gilles Dupuis, Eric H Frost, Anis Larbi, Graham Pawelec, Jacek M Witkowski, Tamas Fulop
Alzheimer's disease is one of the most devastating neurodegenerative diseases. The exact cause of the disease is still not known although many scientists believe in the beta amyloid hypothesis which states that the accumulation of the amyloid peptide beta (Aβ) in brain is the initial cause which consequently leads to pathological neuroinflammation. However, it was recently shown that Aβ may have an important role in defending the brain against infections. Thus, the balance between positive and negative impact of Aβ may determine disease progression...
December 21, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/29273951/neuroinflammatory-responses-in-alzheimer-s-disease
#17
REVIEW
Cira Dansokho, Michael Thomas Heneka
Neuroinflammatory responses in Alzheimer's disease (AD) are complex and not fully understood. They involve various cellular and molecular players and associate interaction between the central nervous system (CNS) and the periphery. Amyloid peptides within the senile plaques and abnormally phosphorylated tau in neurofibrillary tangles are able to initiate inflammatory responses, in brain of AD patients and in mouse models of this disease. The outcome of these responses on the pathophysiology of AD depends on several factors and can be either beneficial or detrimental...
December 22, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/29273047/donepezil-suppresses-intracellular-ca2-mobilization-through-the-pi3k-pathway-in-rodent-microglia
#18
Yoshinori Haraguchi, Yoshito Mizoguchi, Masahiro Ohgidani, Yoshiomi Imamura, Toru Murakawa-Hirachi, Hiromi Nabeta, Hiroshi Tateishi, Takahiro A Kato, Akira Monji
BACKGROUND: Microglia are resident innate immune cells which release many factors including proinflammatory cytokines or nitric oxide (NO) when they are activated in response to immunological stimuli. Pathophysiology of Alzheimer's disease (AD) is related to the inflammatory responses mediated by microglia. Intracellular Ca2+ signaling is important for microglial functions such as release of NO and cytokines. In addition, alteration of intracellular Ca2+ signaling underlies the pathophysiology of AD, while it remains unclear how donepezil, an acetylcholinesterase inhibitor, affects intracellular Ca2+ mobilization in microglial cells...
December 22, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29259854/microglia-express-abi3-in-the-brains-of-alzheimer-s-disease-and-nasu-hakola-disease
#19
Jun-Ichi Satoh, Yoshihiro Kino, Motoaki Yanaizu, Youhei Tosaki, Kenji Sakai, Tsuyoshi Ishida, Yuko Saito
Nasu-Hakola disease (NHD) is a rare autosomal recessive leukoencephalopathy caused by a loss-of-function mutation of either TYROBP (DAP12) or TREM2 expressed in microglia. A rare variant of the TREM2 gene encoding p.Arg47His causes a 3-fold increase in the risk for late-onset Alzheimer's disease (LOAD). A recent study demonstrated that a rare coding variant p.Ser209Phe in the ABI family member 3 (ABI3) gene, a regulator of actin cytoskeleton organization, confers risk of developing of LOAD, although the pattern of ABI3 expression in AD and NHD brains with relevance to microglial pathology remains to be characterized...
November 2017: Intractable & Rare Diseases Research
https://www.readbyqxmd.com/read/29258283/astragalus-membranaceus-polysaccharides-ameliorates-obesity-hepatic-steatosis-neuroinflammation-and-cognition-impairment-without-affecting-amyloid-deposition-in-metabolically-stressed-appswe-ps1de9-mice
#20
Yung-Cheng Huang, Huey-Jen Tsay, Mei-Kuang Lu, Chien-Hung Lin, Chih-Wen Yeh, Hui-Kang Liu, Young-Ji Shiao
Astragalus membranaceus is commonly used in traditional Chinese medicine for strengthening the host defense system. Astragalus membranaceus-polysaccharides is an effective component with various important bioactivities, such as immunomodulation, antioxidant, anti-diabetes, anti-inflammation and neuroprotection. In the present study, we determine the effects of Astragalus membranaceus-polysaccharides on metabolically stressed transgenic mice in order to develop this macromolecules for treatment of sporadic Alzheimer's disease, a neurodegenerative disease with metabolic risk factors...
December 18, 2017: International Journal of Molecular Sciences
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