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Alzheimer inflammation

Annamaria Cattaneo, Nadia Cattane, Samantha Galluzzi, Stefania Provasi, Nicola Lopizzo, Cristina Festari, Clarissa Ferrari, Ugo Paolo Guerra, Barbara Paghera, Cristina Muscio, Angelo Bianchetti, Giorgio Dalla Volta, Marinella Turla, Maria Sofia Cotelli, Michele Gennuso, Alessandro Prelle, Orazio Zanetti, Giulia Lussignoli, Dario Mirabile, Daniele Bellandi, Simona Gentile, Gloria Belotti, Daniele Villani, Taoufiq Harach, Tristan Bolmont, Alessandro Padovani, Marina Boccardi, Giovanni B Frisoni
The pathway leading from amyloid-β deposition to cognitive impairment is believed to be a cornerstone of the pathogenesis of Alzheimer's disease (AD). However, what drives amyloid buildup in sporadic nongenetic cases of AD is still unknown. AD brains feature an inflammatory reaction around amyloid plaques, and a specific subset of the gut microbiota (GMB) may promote brain inflammation. We investigated the possible role of the GMB in AD pathogenesis by studying the association of brain amyloidosis with (1) GMB taxa with pro- and anti-inflammatory activity; and (2) peripheral inflammation in cognitively impaired patients...
August 31, 2016: Neurobiology of Aging
Chatchai Muanprasat, Varanuj Chatsudthipong
Chitosan oligosaccharide (COS) is an oligomer of β-(1➔4)-linked D-glucosamine. COS can be prepared from the deacetylation and hydrolysis of chitin, which is commonly found in the exoskeletons of arthropods and insects and the cell walls of fungi. COS is water soluble, non-cytotoxic, readily absorbed through the intestine and mainly excreted in the urine. Of particular importance, COS and its derivatives have been demonstrated to possess several biological activities including anti-inflammation, immunostimulation, anti-tumor, anti-obesity, anti-hypertension, anti-Alzheimer's disease, tissue regeneration promotion, drug and DNA delivery enhancement, anti-microbial, anti-oxidation and calcium-absorption enhancement...
October 20, 2016: Pharmacology & Therapeutics
Porcelli Stefano, Crisafulli Concetta, Donato Luigi, Calabrò Marco, Politis Antonis, Liappas Ioannis, Albani Diego, Atti Anna Rita, Salfi Raffaele, Raimondi Ilaria, Forloni Gianluigi, Papadimitriou George N, De Ronchi Diana, Serretti Alessandro
INTRODUCTION: With the increase of the population's average age, Alzheimer's disease (AD) is becoming one of the most disabling diseases worldwide. Recently, neurodevelopment processes have been involved in the AD etiopathogenesis. Genetic studies in this field could contribute to our knowledge and suggest new molecular targets for possible treatments. METHODS: Our primary aim was to investigate the associations among single nucleotide polymorphisms (SNPs) within neurodevelopment related genes (BDNF, ST8SIA2, C15orf32, NCAPG2, ESYT2, WDR60, LOC154822, VIPR2, GSK3B, NR1I2, ZNF804A, SP4) and AD...
November 15, 2016: Journal of the Neurological Sciences
Mercedes Garcia-Gil, Elisabetta Albi
In the last 20 years it has been widely demonstrated that cell nucleus contains neutral and polar lipids localized in nuclear membranes, nucleoli, nuclear matrix and chromatin. Nuclear lipids may show specific organization forming nuclear lipid microdomains and have both structural and functional roles. Depending on their localization, nuclear lipids play different roles such as the regulation of nuclear membrane and nuclear matrix fluidity but they also can act as platforms for vitamin and hormone function, for active chromatin anchoring, and for the regulation of gene expression, DNA duplication and transcription...
October 20, 2016: Neurochemical Research
Jian Yang, Jing Yang, Steven H Liang, Yungen Xu, Anna Moore, Chongzhao Ran
In brains of Alzheimer's disease (AD), reactive oxygen species (ROS) levels are significantly higher than that of healthy brains. Evidence suggests that, during AD onset and progression, a vicious cycle revolves around amyloid beta (Aβ) production, aggregation, plaque formation, microglia/immunological responses, inflammation, and ROS production. In this cycle, ROS species play a central role, and H2O2 is one of the most important ROS species. In this report, we have designed a fluorescent imaging probe CRANAD-88, which is capable of cascade amplifying near infrared fluorescence (NIRF) signals at three levels upon interacting with H2O2 in AD brains...
October 20, 2016: Scientific Reports
FangFang, Hongyan Li, Tingting Qin, Min Li, Shiping Ma
The impaired insulin signaling has been recognized as a common pathogenetic mechanism between diabetes and Alzheimer's disease (AD). In the progression of AD, brain is characterized by defective insulin receptor substrate-1 (IRS-1) and increased oxidative stress. Thymol, a monoterpene phenol isolated from medicinal herbs, has exhibited robust neuroprotective effects. The present study was designed to investigate the protective effect of thymol on HFD-induced cognitive deficits, and explore the possible mechanisms...
October 20, 2016: Metabolic Brain Disease
Tomoyuki Masuda, Junko Itoh, Takuya Koide, Yasushi Tomidokoro, Yosuke Takei, Kazuhiro Ishii, Akira Tamaoka
A chronic inflammatory condition may underlie neurodegenerative disorders, including Parkinson's disease (PD) and Alzheimer's disease (AD). For example, both PD and AD patients show an increase in transforming growth factor-β1 (TGF-β1) levels in their cerebrospinal fluid (CSF). TGF-β1 is a cytokine that inhibits inflammation. In the present study, using an enzyme-linked immunosorbent assay, we tested the hypothesis that the level of TGF-β1 in the CSF of patients with amyotrophic lateral sclerosis (ALS), spinocerebellar degeneration (SCD), or multiple system atrophy-cerebellar subtype (MSA-C) would be elevated compared with that of normal controls...
October 15, 2016: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
Shokei Kim-Mitsuyama
There is accumulating evidence that RAS inhibitors not only reduce blood pressure, but also exert pleiotropic effects, including a renoprotective effect, amelioration of insulin resistance, reduction in onset of diabetes, and suppression of cardiovascular remodelling,. However, the definite benefit of RAS inhibition in treatment of hypertension with CKD or DM is not conclusive. We previously performed the OlmeSartan and Calcium Antagonists Randomized (OSCAR) study comparing the preventive effect of high-dose ARB therapy versus ARB plus CCB combination therapy on cardiovascular morbidity and mortality in 1164 Japanese elderly hypertensive patients with baseline type 2 diabetes and/or CVD (Am J Med (2012))...
September 2016: Journal of Hypertension
Huiting Su, Ning Na, Xiaodong Zhang, Yong Zhao
CD74 (MHC class II invariant chain, Ii) is a non-polymorphic type II transmembrane glycoprotein. It is clear that, in addition to be an MHC class II chaperone, CD74 has a diversity of biological functions in physiological and pathological situations. CD74 also participates in other non-MHC II protein trafficking, such as angiotensin II type I receptor. In addition, CD74 is a cell membrane high-affinity receptor for macrophage migration inhibitory factor (MIF), D-dopachrome tautomerase (D-DT/MIF-2) and bacterial proteins...
October 17, 2016: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
Claudia Balducci, Angelisa Frasca, Margherita Zotti, Pietro La Vitola, Emanuela Mhillaj, Emanuele Grigoli, Martina Iacobellis, Federica Grandi, Massimo Messa, Laura Colombo, Monica Molteni, Luigia Trabace, Carlo Rossetti, Mario Salmona, Gianluigi Forloni
[Background] Amyloid-β oligomers (AβO) are species mainly involved in the synaptic and cognitive dysfunction in Alzheimer's disease. Although their action has been described mainly at neuronal level, it is now clear that glial cells govern synaptic activity in their resting state, contributing to new learning and memory establishment. In contrast, when activated, they may lead to synaptic and cognitive dysfunction. Using a reliable acute AβO-mediated mouse model of AD, we explored whether the memory alteration AβOs induce relies on the activation of glial cells, and if Toll-like receptor 4 (TLR4), pivotal in the initiation of an immune response, is involved...
October 14, 2016: Brain, Behavior, and Immunity
Marie-Laure Specq, Mélisande Bourgoin-Heck, Nathalie Samson, François Corbin, Christian Gestreau, Maxime Richer, Hazim Kadhim, Jean-Paul Praud
Hyperbilirubinemia (HB) occurs in 90% of preterm newborns. Moderate HB can induce acute neurological disorders while severe HB has been linked to a higher incidence of apneas of prematurity. The present study aimed to test the hypothesis that even moderate HB disrupts cardiorespiratory control in preterm lambs. Two groups of preterm lambs (born 14 days prior to term), namely control (n = 6) and HB (n = 5), were studied. At day 5 of life, moderate HB (150-250 μmol/L) was induced during 17 h in the HB group after which cardiorespiratory control as well as laryngeal and pulmonary chemoreflexes were assessed during baseline recordings and during hypoxia...
2016: Frontiers in Physiology
E M Ribe, S Lovestone
As populations across the world both age and become more obese, the numbers of individuals with Alzheimer's disease and diabetes are increasing; posing enormous challenges for society and consequently becoming priorities for governments and global organizations. These issues, an ageing population at risk of neurodegenerative diseases such as Alzheimer's disease and an increasingly obese population at risk of metabolic alterations such as type 2 diabetes, are usually considered as independent conditions, but increasing evidence from both epidemiological and molecular studies link these disorders...
October 14, 2016: Journal of Internal Medicine
Koji Hori, Kimiko Konishi, Misa Hosoi, Hiroi Tomioka, Masayuki Tani, Yuka Kitajima, Mitsugu Hachisu
Given the relationship between anticholinergic activity (AA) and Alzheimer's disease (AD), we rereview our hypothesis of the endogenous appearance of AA in AD. Briefly, because acetylcholine (ACh) regulates not only cognitive function but also the inflammatory system, when ACh downregulation reaches a critical level, inflammation increases, triggering the appearance of cytokines with AA. Moreover, based on a case report of a patient with mild AD and slightly deteriorated ACh, we also speculate that AA can appear endogenously in Lewy body disease due to the dual action of the downregulation of ACh and hyperactivity of the hypothalamic-pituitary-adrenal axis...
2016: Parkinson's Disease
Walter J Lukiw
The human microbiome consists of ~3.8 × 10(13) symbiotic microorganisms that form a highly complex and dynamic ecosystem: the gastrointestinal (GI) tract constitutes the largest repository of the human microbiome by far, and its impact on human neurological health and disease is becoming increasingly appreciated. Bacteroidetes, the largest phylum of Gram-negative bacteria in the GI tract microbiome, while generally beneficial to the host when confined to the GI tract, have potential to secrete a remarkably complex array of pro-inflammatory neurotoxins that include surface lipopolysaccharides (LPSs) and toxic proteolytic peptides...
2016: Frontiers in Microbiology
Patrick L McGeer, Joseph Rogers, Edith G McGeer
Two basic discoveries spurred research into inflammation as a driving force in the pathogenesis of Alzheimer's disease (AD). The first was the identification of activated microglia in association with the lesions. The second was the discovery that rheumatoid arthritics, who regularly consume anti-inflammatory agents, were relatively spared from the disease. These findings led to an exploration of the inflammatory pathways that were involved in AD pathogenesis. A pivotal advance was the discovery that amyloid-β protein (Aβ) activated the complement system...
October 4, 2016: Journal of Alzheimer's Disease: JAD
Ashley N Nilson, Kelsey C English, Julia E Gerson, T Barton Whittle, C Nicolas Crain, Judy Xue, Urmi Sengupta, Diana L Castillo-Carranza, Wenbo Zhang, Praveena Gupta, Rakez Kayed
It is well-established that inflammation plays an important role in Alzheimer's disease (AD) and frontotemporal lobar dementia (FTLD). Inflammation and synapse loss occur in disease prior to the formation of larger aggregates, but the contribution of tau to inflammation has not yet been thoroughly investigated. Tau pathologically aggregates to form large fibrillar structures known as tangles. However, evidence suggests that smaller soluble aggregates, called oligomers, are the most toxic species and form prior to tangles...
October 1, 2016: Journal of Alzheimer's Disease: JAD
Francisca Cornejo, Rommy von Bernhardi
As we age, a large number of physiological and molecular changes affect the normal functioning of cells, tissues, and the organism as a whole. One of the main changes is the establishment of a state of systemic inflammatory activation, which has been termed "inflamm-aging"; a mild chronic inflammation of the aging organism that reduces the ability to generate an efficient response against stressor stimuli. As any other system, the nervous system undergoes these aging-related changes; the neuroinflammatory state depends mainly on the dysregulated activation of microglia, the innate immune cells of the central nervous system (CNS) and the principal producers of reactive oxygen species...
2016: Advances in Experimental Medicine and Biology
Dilek Colak, Ayodele A Alaiya, Namik Kaya, Nzioka P Muiya, Olfat AlHarazi, Zakia Shinwari, Editha Andres, Nduna Dzimiri
AIMS: The disease pathways leading to idiopathic dilated cardiomyopathy (DCM) are still elusive. The present study investigated integrated global transcriptional and translational changes in human DCM for disease biomarker discovery. METHODS: We used identical myocardial tissues from five DCM hearts compared to five non-failing (NF) donor hearts for both transcriptome profiling using the ABI high-density oligonucleotide microarrays and proteome expression with One-Dimensional Nano Acquity liquid chromatography coupled with tandem mass spectrometry on the Synapt G2 system...
2016: PloS One
Boris Decourt, Debomoy K Lahiri, Marwan N Sabbagh
Alzheimer's disease (AD) affects an estimated 44 million individuals worldwide, yet no therapeutic intervention is available to stop the progression of the dementia. Neuropathological hallmarks of AD are extracellular deposits of amyloid beta (Aβ) peptides into plaques, intraneuronal accumulation of hyperphosphorylated tau protein forming tangles, and chronic inflammation. A pivotal molecule in inflammation is the pro-inflammatory cytokine TNF-α. Several lines of evidence using genetic and pharmacological manipulations indicate that TNF-α signaling exacerbates both Aβ and tau pathologies in vivo...
September 30, 2016: Current Alzheimer Research
Katarina Spilovska, Jan Korabecny, Eugenie Nepovimova, Rafael Dolezal, Eva Mezeiova, Ondrej Soukup, Kamil Kuca
Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder. Several hallmarks such as β-amyloid (Aβ) aggregation underlying amyloid plaque formation, τ-hyperphosphorylation leading to the production of neurofibrillary tangles, and decline in the number of cholinergic neurons appear to be fundamental in the pathophysiology of the disease. Other evidence points also to the involvement of oxidative stress, biometal dyshomeostasis, inflammation, and cell cycle regulatory failure. Taking into account such premises, many attractive targets for the development of anti-AD drugs have emerged...
September 27, 2016: Current Topics in Medicinal Chemistry
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