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https://www.readbyqxmd.com/read/29050859/neuroprotective-effects-of-a-triple-glp-1-gip-glucagon-receptor-agonist-in-the-app-ps1-transgenic-mouse-model-of-alzheimer-s-disease
#1
Jingjing Tai, Weizhen Liu, Yanwei Li, Lin Li, Christian Hölscher
Type 2 diabetes mellitus (T2DM) is a risk factor for Alzheimer disease (AD). Previous studies have shown that the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) that have anti-diabetic properties show very promising effects in animal models of AD. Glucagon (Gcg) is a hormone and growth-factor, and the Gcg receptor is expressed in the brain. Here we test the effects of a triple receptor agonist (TA), which activates GIP-1, GIP and glucagon receptors at the same time...
October 16, 2017: Brain Research
https://www.readbyqxmd.com/read/29050210/astaxanthin-acts-via-lrp-1-to-inhibit-inflammation-and-reverse-lipopolysaccharide-induced-m1-m2-polarization-of-microglial-cells
#2
Xiaojun Wen, Lijiao Xiao, Zhuoyan Zhong, Limin Wang, Ze Li, Xiaoping Pan, Zhonglin Liu
Microglia become activated during neuroinflammation and produce neurotoxic and neurotrophic factors, depending on whether they acquire M1 proinflammatory or M2 anti-inflammatory phenotypes. Astaxanthin (ATX), a natural carotenoid, has anti-inflammatory and neuroprotective effects. We investigated whether ATX could reverse M1/M2 polarization and suppress neuroinflammation via low-density lipoprotein receptor-related protein-1 (LRP-1). We observed increased expression of M1 (TNF-α, IL-1β, and CD86) and decreased expression of M2 (Arg-1, IL-10, and CD206) markers in BV2 microglial cells stimulated with lipopolysaccharide (LPS)...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29044639/inflammatory-pathology-markers-activated-microglia-and-reactive-astrocytes-in-early-and-late-onset-alzheimer-disease-a-post-mortem-study
#3
Ricardo Taipa, Vitor Ferreira, Paulo Brochado, Andrew Robinson, Inês Reis, Fernanda Marques, David M Mann, Manuel Melo Pires, Nuno Sousa
AIMS: The association between the pathological features of AD and dementia is stronger in younger old persons than in older old persons suggesting that additional factors are involved in the clinical expression of dementia in the oldest old. Cumulative data suggests that neuroinflammation plays a prominent role in Alzheimer's disease (AD) and different studies reported an age-associated dysregulation of the neuroimmune system. Consequently, we sought to characterize the pattern of microglial cell activation and astrogliosis in brain post-mortem tissue of pathologically confirmed cases of early and late onset AD (EOAD and LOAD) and determine their relation to age...
October 17, 2017: Neuropathology and Applied Neurobiology
https://www.readbyqxmd.com/read/29044416/disease-and-region-specificity-of-granulin-immunopositivities-in-alzheimer-disease-and-frontotemporal-lobar-degeneration
#4
Qinwen Mao, Dongyang Wang, Yanqing Li, Missia Kohler, Jayson Wilson, Zachary Parton, Bella Shmaltsuyeva, Demirkan Gursel, Rosa Rademakers, Sandra Weintraub, Marek-Marsel Mesulam, Haibin Xia, Eileen H Bigio
Heterozygous loss-of-function mutations in GRN, the progranulin gene, which result in progranulin (PGRN) protein haploinsufficiency, are a major cause of frontotemporal lobar degeneration with TDP-43 proteinopathy (FTLD-TDP). PGRN is composed of seven and a half repeats of a highly conserved granulin motif that is cleaved to produce the granulin peptides A-G and paragranulin. To better understand the role of PGRN and granulin (Grn) peptides in the pathogenesis of neurodegeneration, we evaluated PGRN/Grn in brains of patients with Alzheimer disease, FTLD-TDP type A with or without GRN mutations, and normal individuals, using a panel of monoclonal antibodies against Grn peptides A-G...
November 1, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/29038051/integrated-approach-reveals-diet-apoe-genotype-and-sex-affect-immune-response-in-app-mice
#5
Kyong Nyon Nam, Cody M Wolfe, Nicholas F Fitz, Florent Letronne, Emilie L Castranio, Anais Mounier, Jonathan Schug, Iliya Lefterov, Radosveta Koldamova
Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder that is influenced by genetic and environmental risk factors, such as inheritance of ε4 allele of APOE (APOE4), sex and diet. Here, we examined the effect of high fat diet (HFD) on amyloid pathology and expression profile in brains of AD model mice expressing human APOE isoforms (APP/E3 and APP/E4 mice). APP/E3 and APP/E4 mice were fed HFD or Normal diet for 3months. We found that HFD significantly increased amyloid plaques in male and female APP/E4, but not in APP/E3 mice...
October 13, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29036636/genetic-reduction-of-nrf2-exacerbates-cognitive-deficits-in-a-mouse-model-of-alzheimer-s-disease
#6
Caterina Branca, Eric Ferreira, Thuy-Vi Nguyen, Kristian Doyle, Antonella Caccamo, Salvatore Oddo
Aging is the major risk factor for several neurodegenerative diseases, including Alzheimer's disease (AD). However, the mechanisms by which aging contributes to neurodegeneration remain elusive. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a transcription factor that regulates expression of a vast number of genes by binding to the antioxidant response element. Nrf2 levels decrease as a function of age, and reduced Nrf2 levels have been reported in postmortem human brains and animal models of AD...
September 19, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29027011/let-s-make-microglia-great-again-in-neurodegenerative-disorders
#7
REVIEW
Marie-Victoire Guillot-Sestier, Terrence Town
All of the common neurodegenerative disorders-Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and prion diseases-are characterized by accumulation of misfolded proteins that trigger activation of microglia; brain-resident mononuclear phagocytes. This chronic form of neuroinflammation is earmarked by increased release of myriad cytokines and chemokines in patient brains and biofluids. Microglial phagocytosis is compromised early in the disease process, obfuscating clearance of abnormal proteins...
October 12, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/29026707/nadph-oxidase-mediates-%C3%AE-amyloid-peptide-induced-neuronal-death-in-mouse-cortical-cultures
#8
Kee-Oh Chay, Kyoung Young Nam Koong, Shinae Hwang, Jong-Keun Kim, Choon Sang Bae
β-Amyloid peptide (Aβ) is the main component of senile plaques in patients with Alzheimer's disease, and is known to be a main pathogenic factor of the disease. Recent evidence indicates that activation of NADPH oxidase (NOX) in microglia or astrocytes may be a source of Aβ-induced reactive oxygen species (ROS). We investigated the role of neuronal NOX in Aβ-induced neuronal death in mouse mixed cortical cultures. Cell death was assessed by measuring lactate dehydrogenase efflux to bathing media 24 or 48 hr after exposure to Aβ25-35, a fragment of Aβ with an equivalent neurotoxic effect...
September 2017: Chonnam Medical Journal
https://www.readbyqxmd.com/read/29023416/neuro-coagulopathy-blood-coagulation-factors-in-central-nervous-system-diseases
#9
REVIEW
Ciro De Luca, Assunta Virtuoso, Nicola Maggio, Michele Papa
Blood coagulation factors and other proteins, with modulatory effects or modulated by the coagulation cascade have been reported to affect the pathophysiology of the central nervous system (CNS). The protease-activated receptors (PARs) pathway can be considered the central hub of this regulatory network, mainly through thrombin or activated protein C (aPC). These proteins, in fact, showed peculiar properties, being able to interfere with synaptic homeostasis other than coagulation itself. These specific functions modulate neuronal networks, acting both on resident (neurons, astrocytes, and microglia) as well as circulating immune system cells and the extracellular matrix...
October 12, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29020624/temporal-tracking-of-microglia-activation-in-neurodegeneration-at-single-cell-resolution
#10
Hansruedi Mathys, Chinnakkaruppan Adaikkan, Fan Gao, Jennie Z Young, Elodie Manet, Martin Hemberg, Philip L De Jager, Richard M Ransohoff, Aviv Regev, Li-Huei Tsai
Microglia, the tissue-resident macrophages in the brain, are damage sensors that react to nearly any perturbation, including neurodegenerative diseases such as Alzheimer's disease (AD). Here, using single-cell RNA sequencing, we determined the transcriptome of more than 1,600 individual microglia cells isolated from the hippocampus of a mouse model of severe neurodegeneration with AD-like phenotypes and of control mice at multiple time points during progression of neurodegeneration. In this neurodegeneration model, we discovered two molecularly distinct reactive microglia phenotypes that are typified by modules of co-regulated type I and type II interferon response genes, respectively...
October 10, 2017: Cell Reports
https://www.readbyqxmd.com/read/28994715/%C3%AE-amyloid-and-the-pathomechanisms-of-alzheimer-s-disease-a-comprehensive-view
#11
REVIEW
Botond Penke, Ferenc Bogár, Lívia Fülöp
Protein dyshomeostasis is the common mechanism of neurodegenerative diseases such as Alzheimer's disease (AD). Aging is the key risk factor, as the capacity of the proteostasis network declines during aging. Different cellular stress conditions result in the up-regulation of the neurotrophic, neuroprotective amyloid precursor protein (APP). Enzymatic processing of APP may result in formation of toxic Aβ aggregates (β-amyloids). Protein folding is the basis of life and death. Intracellular Aβ affects the function of subcellular organelles by disturbing the endoplasmic reticulum-mitochondria cross-talk and causing severe Ca(2+)-dysregulation and lipid dyshomeostasis...
October 10, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28991528/protosappanin-a-exerts-anti-neuroinflammatory-effect-by-inhibiting-jak2-stat3-pathway-in-lipopolysaccharide-induced-bv2-microglia
#12
Li-Chao Wang, Li-Xi Liao, Ming-Bo Zhao, Xin Dong, Ke-Wu Zeng, Peng-Fei Tu
Microglial activation and resultant neuroinflammatory response are implicated in various brain diseases including Alzheimer's disease and Parkinson's disease. Treatment with anti-neuroinflammatory agents could provide therapeutic benefits for such disorders. Protosappanin A (PTA) is a major bioactive ingredient isolated from Caesalpinia sappan L.. In this work, the anti-neuroinflammatory effects of PTA on LPS-stimulated BV2 cells were investigated and the underlying mechanisms were explored. Results showed that PTA significantly inhibited the production of TNF-α and IL-1β in LPS-activated BV2 microglia...
September 2017: Chinese Journal of Natural Medicines
https://www.readbyqxmd.com/read/28987033/trem2-expression-in-the-human-brain-a-marker-of-monocyte-recruitment
#13
Marie Fahrenhold, Sonja Rakic, John Classey, Carol Brayne, Paul G Ince, James A R Nicoll, Delphine Boche
Mutation in the triggering receptor expressed on myeloid cells (TREM) 2 gene has been identified as a risk factor for several neurodegenerative diseases including Alzheimer's disease (AD). Experimental studies using animal models of AD have highlighted a number of functions associated with TREM2 and its expression by microglial cells. It has therefore been assumed that this is also the case in humans. However, there is very limited information concerning the cellular expression of TREM2 in the human brain. As part of investigations of microglia using post-mortem resources provided by the Medical Research Council Cognitive Function and Ageing Studies (MRC-CFAS), we immunostained the cerebral cortex of 299 participants for TREM2 using the Sigma antibody HPA010917 and compared with the macrophage/microglial markers Iba1 and CD68...
October 7, 2017: Brain Pathology
https://www.readbyqxmd.com/read/28986511/neuroinflammation-appears-early-and-then-plateaus-in-a-mouse-model-of-alzheimer-s-disease-shown-by-pet-imaging
#14
Francisco R López-Picón, Anniina Snellman, Olli Eskola, Semi Helin, Olof Solin, Merja Haaparanta-Solin, Juha O Rinne
Rationale: Neuroinflammation has been associated with different neurological diseases including Alzheimer's disease (AD). In AD, the translocator protein 18kDa (TSPO) is overexpressed in the activated microglia that surround the β-amyloid plaques. In the current longitudinal study, using a mouse model of AD, we evaluated the association between β-amyloid deposition and neuroinflammation in AD. Methods: To monitor the longitudinal changes in β-amyloid deposition and neuroinflammation, we used in vivo PET imaging and ex vivo autoradiography with (11)C-PIB and a TSPO tracer, (18)F-GE-180, in the APP23 mouse model of AD...
October 6, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28985759/role-of-microglial-amylin-receptors-in-mediating-beta-amyloid-a%C3%AE-induced-inflammation
#15
Wen Fu, Vlatka Vukojevic, Aarti Patel, Rania Soudy, David MacTavish, David Westaway, Kamaljit Kaur, Valeri Goncharuk, Jack Jhamandas
BACKGROUND: Neuroinflammation in the brain consequent to activation of microglia is viewed as an important component of Alzheimer's disease (AD) pathology. Amyloid beta (Aβ) protein is known to activate microglia and unleash an inflammatory cascade that eventually results in neuronal dysfunction and death. In this study, we sought to identify the presence of amylin receptors on human fetal and murine microglia and determine whether Aβ activation of the inflammasome complex and subsequent release of cytokines is mediated through these receptors...
October 6, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28985224/caspase-8-association-with-alzheimer-s-disease-and-functional-analysis-of-rare-variants
#16
Jan Rehker, Johanna Rodhe, Ryan R Nesbitt, Evan A Boyle, Beth K Martin, Jenny Lord, Ilker Karaca, Adam Naj, Frank Jessen, Seppo Helisalmi, Hilkka Soininen, Mikko Hiltunen, Alfredo Ramirez, Martin Scherer, Lindsay A Farrer, Jonathan L Haines, Margaret A Pericak-Vance, Wendy H Raskind, Carlos Cruchaga, Gerard D Schellenberg, Bertrand Joseph, Zoran Brkanac
The accumulation of amyloid beta (Aβ) peptide (Amyloid cascade hypothesis), an APP protein cleavage product, is a leading hypothesis in the etiology of Alzheimer's disease (AD). In order to identify additional AD risk genes, we performed targeted sequencing and rare variant burden association study for nine candidate genes involved in the amyloid metabolism in 1886 AD cases and 1700 controls. We identified a significant variant burden association for the gene encoding caspase-8, CASP8 (p = 8.6x10-5). For two CASP8 variants, p...
2017: PloS One
https://www.readbyqxmd.com/read/28984087/effects-of-rhei-undulati-rhizoma-on-lipopolysaccharide-induced-neuroinflammation-in-vitro-and-in-vivo
#17
Deok-Sang Hwang, Pil Sung Gu, Namkwon Kim, Young Pyo Jang, Myung Sook Oh
Neuroinflammation plays a critical role in the pathogenesis of degenerative brain diseases such as Alzheimer's disease and Parkinson's disease. Microglia are the major components of the brain immune system that regulate inflammatory processes. Activated microglia release pro-inflammatory factors and cytokines, resulting in neuronal cell death. We focused on inhibiting the activation of microglia from a stimulus as a strategy to search for neuroprotective drugs. Rhei Undulati Rhizoma (RUR) is traditionally used to treat various inflammatory disorders...
October 6, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/28982335/reduced-serotonin-transporter-levels-and-inflammation-in-the-midbrain-raphe-of-12-month-old-appswe-psen1de9-mice
#18
Athanasios Metaxas, Ramanan Vaitheeswaran, Katrine T Jensen, Camilla Thygesen, Laura Ilkjaer, Sultan Darvesh, Bente Finsen
Background Although mood and sleep disturbances are nearly universal among patients with Alzheimer's disease (AD), brain structures involved in non-cognitive processing remain under characterized in terms of AD pathology. Objectives This study was designed to evaluate hallmarks of AD pathology in the brainstem of the APPswe/PS1dE9 mouse model of familial AD. Methods Fresh-frozen sections from female, 12 month old, transgenic and control B6C3 mice (n=6/genotype) were examined for amyloid burden and neurofibrillary alterations, by using 6E10 immunohistochemistry and the Gallyas silver stain, respectively...
October 4, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28978423/trem2-keeping-microglia-fit-during-good-times-and-bad
#19
Soyon Hong, Beth Stevens
Microglia are the macrophages of the brain and play an important role in Alzheimer's disease (AD). In Cell, Ulland et al. (2017) recently reported that mutations in TREM2, a protein implicated in AD, disrupt microglial energy state and function, thus sabotaging the microglia's ability to defend the brain against amyloid plaques.
October 3, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28977782/edaravone-attenuates-the-proinflammatory-response-in-amyloid-%C3%AE-treated-microglia-by-inhibiting-nlrp3-inflammasome-mediated-il-1%C3%AE-secretion
#20
Hong-Mei Wang, Ting Zhang, Jian-Kang Huang, Jing-Yan Xiang, Jing-Jiong Chen, Jian-Liang Fu, Yu-Wu Zhao
BACKGROUND/AIMS: Microglial activation is an important pathological feature in the brains of patients with Alzheimer's disease (AD), and amyloid-β (Aβ) peptides play a crucial role in microglial activation. In addition, edaravone (EDA) was recently shown to suppress oxidative stress and proinflammatory cytokine production in APPswePS1dE9 (APP/PS1) mice. However, the mechanism by which EDA inhibits the Aβ-induced proinflammatory response in microglia is poorly understood. METHODS: The mitochondrial membrane potential (∆ψm) was evaluated using JC-1 staining...
October 5, 2017: Cellular Physiology and Biochemistry
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