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Alzheimers and inflammation

Chye Soi Moi, Chia Kin Yen, Khuen Yen Ng, Koh Rhun Yian
Protein misfolding and aggregation have been considered the common pathological hallmarks for a number of neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD). These abnormal proteins aggregation damage mitochondria and induce oxidative stress and resulting neuronal cell death. Prolong neuronal damage activates microglia and astrocytes, development of inflammation reaction and further promotes neurodegeneration. Thus, elimination of abnormal proteins aggregation without eliciting any adverse effects are the main treatment strategies...
March 15, 2018: CNS & Neurological Disorders Drug Targets
Lisa K Gouwens, Mudar S Ismail, Victoria A Rogers, Nathan T Zeller, Evan C Garrad, Fatima S Amtashar, Nyasha J Makoni, David C Osborn, Michael R Nichols
Microvesicles (MVs) and exosomes comprise a class of cell-secreted particles termed extracellular vesicles (EVs). These cargo-holding vesicles mediate cell-to-cell communication and have recently been implicated in neurodegenerative diseases such as Alzheimer's disease (AD). The two types of EVs are distinguished by the mechanism of cell release and their size, with the smaller exosomes and the larger MVs ranging from 30 to 100 nm and 100 nm to 1 μm in diameter, respectively. MV numbers are increased in AD and appear to interact with amyloid-β peptide (Aβ), the primary protein component of the neuritic plaques in the AD brain...
March 15, 2018: ACS Chemical Neuroscience
Manuel van Gijsel-Bonnello, Kévin Baranger, Philippe Benech, Santiago Rivera, Michel Khrestchatisky, Max de Reggi, Bouchra Gharib
[This corrects the article DOI: 10.1371/journal.pone.0175369.].
2018: PloS One
Yicai Xiao, Gaofeng Li, Yujie Chen, Yuchun Zuo, Kauthar Rashid, Tibiao He, Hua Feng, John H Zhang, Fei Liu
Iatrogenic brain injury inevitably occurs in neurosurgical operations, leading to brain edema, ischemia, intracranial hematoma, and other postoperative complications, eventually worsening neurological outcomes of patients. If apoptotic cells are not rapidly eliminated by phagocytic engulfment, they may communicate with surrounding cells to undergo secondary necrosis and releasing toxic signals. Recent studies have shown that milk fat globule-epidermal growth factor-8 (MFGE8), which promotes phagocytosis and inhibits inflammation, is an endogenous protective factor in response to brain infarction, Alzheimer's disease, subarachnoid hemorrhage, and prion disease...
2018: Frontiers in Neurology
Zhuo Wang, Ya-Hong Zhang, Chuang Guo, Hui-Ling Gao, Man-Li Zhong, Ting-Ting Huang, Na-Na Liu, Rui-Fang Guo, Tian Lan, Wei Zhang, Zhan-You Wang, Pu Zhao
Although the positive relationship between copper and Alzheimer's disease (AD) was reported by a lot of epidemiological data, the mechanism is not completely known. Copper is a redox metal and serves as a mediator of inflammation. Because the homeostasis of copper is altered in Aβ precursor protein (APP) and presenilin 1 (PS1) transgenic (Tg) mice, the using of copper chelators is a potential therapeutic strategy for AD. Here we report that a copper chelator, tetrathiomolybdate (TM), is a potential therapeutic drug of AD...
2018: Frontiers in Aging Neuroscience
Seon Choe, Mudan Cai, Ui Min Jerng, Jun-Hwan Lee
Cognitive impairment is age-related and manageable only with early diagnosis and prevention. Moxibustion is widely accepted in East Asia as useful for preventing cognitive impairment. This systematic review of animal studies was conducted to verify the efficacy of moxibustion in preventing cognitive impairment and to elucidate the underlying mechanism. Randomized controlled animal trials that established the efficacy of moxibustion in preventing cognitive impairment were included in the analysis. Results of behavioral tests and the signaling pathways elucidated were extracted and a meta-analysis was conducted with the behavioral test results...
February 2018: Experimental Neurobiology
Santa Mammana, Paolo Fagone, Eugenio Cavalli, Maria Sofia Basile, Maria Cristina Petralia, Ferdinando Nicoletti, Placido Bramanti, Emanuela Mazzon
In physiological conditions, different types of macrophages can be found within the central nervous system (CNS), i.e., microglia, meningeal macrophages, and perivascular (blood-brain barrier) and choroid plexus (blood-cerebrospinal fluid barrier) macrophages. Microglia and tissue-resident macrophages, as well as blood-borne monocytes, have different origins, as the former derive from yolk sac erythromyeloid precursors and the latter from the fetal liver or bone marrow. Accordingly, specific phenotypic patterns characterize each population...
March 13, 2018: International Journal of Molecular Sciences
Tahereh Farkhondeh, Saeed Samarghandian, Hanieh Shaterzadeh Yazdi, Fariborz Samini
Flavonoids have been used in traditional medicine to promote human health. Crocin has been proposed to be effective in the management of the various diseases including the neurodegenerative diseases. Antiepileptic and anti-Alzheimer effects of crocin have also been indicated. The efficacy of crocis in the treatment of cerebral ischemia and traumatic brain injury was also confirmed by using animal models. Crocin treatment increased dopamine levels in the brain of experimental model of Parkinson's disease. In addition, crocin modulates the opioid system to decrease the withdrawal syndrome...
2018: American Journal of Neurodegenerative Disease
Kyoung A Jhang, Jin-Sun Park, Hee-Sun Kim, Young Hae Chong
BACKGROUND: Mer tyrosine kinase (MerTK) activity necessary for amyloid-stimulated phagocytosis strongly implicates that MerTK dysregulation might contribute to chronic inflammation implicated in Alzheimer's disease (AD) pathology. However, the precise mechanism involved in the regulation of MerTK expression by amyloid-β (Aβ) in proinflammatory environment has not yet been ascertained. METHODS: The objective of this study was to determine the underlying mechanism involved in Aβ-mediated decrease in MerTK expression through Aβ-mediated regulation of MerTK expression and its modulation by sulforaphane in human THP-1 macrophages challenged with Aβ1-42...
March 12, 2018: Journal of Neuroinflammation
Jessica M de Souza, Bruno D C Goncalves, Marcus V Gomez, Luciene B Vieira, Fabiola M Ribeiro
Neurodegenerative diseases affect millions of individuals worldwide. So far, no disease-modifying drug is available to treat patients, making the search for effective drugs an urgent need. Neurodegeneration is triggered by the activation of several cellular processes, including oxidative stress, mitochondrial impairment, neuroinflammation, aging, aggregate formation, glutamatergic excitotoxicity, and apoptosis. Therefore, many research groups aim to identify drugs that may inhibit one or more of these events leading to neuronal cell death...
2018: Frontiers in Pharmacology
Gaia Botteri, Laia Salvadó, Anna Gumà, D Lee Hamilton, Paul J Meakin, Gemma Montagut, Michael L J Ashford, Victoria Ceperuelo-Mallafré, Sonia Fernández-Veledo, Joan Vendrell, María Calderón-Dominguez, Dolors Serra, Laura Herrero, Javier Pizarro, Emma Barroso, Xavier Palomer, Manuel Vázquez-Carrera
OBJECTIVE: β-secretase/β-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1) is a key enzyme involved in Alzheimer's disease that has recently been implicated in insulin-independent glucose uptake in myotubes. However, it is presently unknown whether BACE1 and the product of its activity, soluble APPβ (sAPPβ), contribute to lipid-induced inflammation and insulin resistance in skeletal muscle cells. MATERIALS/METHODS: Studies were conducted in mouse C2C12 myotubes, skeletal muscle from Bace1-/- mice and mice treated with sAPPβ and adipose tissue and plasma from obese and type 2 diabetic patients...
March 8, 2018: Metabolism: Clinical and Experimental
Csaba Fekete, Csaba Vastagh, Ádám Dénes, Erik Hrabovszky, Gábor Nyiri, Imre Kalló, Zsolt Liposits, Miklós Sárvári
Microglia are instrumental for recognition and elimination of amyloid β1-42 oligomers (AβO), but the long-term consequences of AβO-induced inflammatory changes in the brain are unclear. Here, we explored microglial responses and transciptome-level inflammatory signatures in the rat hippocampus after chronic AβO challenge. Middle-aged Long Evans rats received intracerebroventricular infusion of AβO or vehicle for 4 weeks, followed by treatment with artificial CSF or MCC950 for the subsequent 4 weeks. AβO infusion evoked a sustained inflammatory response including activation of NF-κB, triggered microglia activation and increased the expression of pattern recognition and phagocytic receptors...
March 6, 2018: Neuroscience
Souravh Bais, Renu Kumari, Yash Prashar
BACKGROUND: sinapic acid (3, 5 di-methoxy 4-hydroxycinnamic acid) is a bioactive compound. Recent studies showed that it has a significant potential to attenuate various chemically induced Neurodegenerative toxicities. AIM: the present study investigates the potential of sinapic acid as neuromodulator and its effect on release of Monoamine Oxidase (MAO-A, MAO-B), TNF-α, Acetylcholine esterase Enzyme, in cognitive dysfunctions associated with experimental dementia...
March 9, 2018: CNS & Neurological Disorders Drug Targets
Jodie Stephenson, Erik Nutma, Paul van der Valk, Sandra Amor
Neurodegenerative diseases, the leading cause of morbidity and disability is gaining increased attention as it imposes a considerable socioeconomic impact, due in part to the ageing community. Neuronal damage is a pathological hallmark of Alzheimer's and Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, spinocerebellar ataxia and multiple sclerosis, although such damage is also observed following neurotropic viral infections, stroke, genetic white matter diseases and paraneoplastic disorders...
March 7, 2018: Immunology
Jianping Wang, Yamin Zhang
Berberine has multiple clinical applications, including the treatment of tumors, diabetes, cardiovascular diseases, hyperlipidemia, inflammation, bacterial and viral infections, cerebral ischemic injuries, mental diseases, Alzheimer's disease and osteoporosis. In the present study, the neuroprotective effect of berberine agonist rescue learning and memory in severe traumatic brain injury (TBI), and the possible mechanism underlying these observations was explored. The protective effect of berberine agonist significantly recovered learning and memory skills, attenuated brain edema and inhibited matrix metalloproteinase‑3 and ‑9 protein expression in mice with severe TBI...
March 5, 2018: Molecular Medicine Reports
Ismini C Mainta, Maria I Vargas, Sara Trombella, Giovanni B Frisoni, Paul G Unschuld, Valentina Garibotto
Multiple factors, namely amyloid, tau, inflammation, metabolic, and perfusion changes, contribute to the cascade of neurodegeneration and functional decline occurring in Alzheimer's disease (AD). These molecular and cellular processes and related functional and morphological changes can be visualized in vivo by two imaging modalities, namely positron emission tomography (PET) and magnetic resonance imaging (MRI). These imaging biomarkers are now part of the diagnostic algorithm and of particular interest for patient stratification and targeted drug development...
2018: Methods in Molecular Biology
Bianca A Trombetta, Becky C Carlyle, Aaron M Koenig, Leslie M Shaw, John Q Trojanowski, David A Wolk, Joseph J Locascio, Steven E Arnold
OBJECTIVE: Alzheimer's disease (AD) is a complex neurodegenerative disease driven by multiple interacting pathophysiological processes that ultimately results in synaptic loss, neuronal death, and dementia. We implemented a fit-for-purpose modeled approach to qualify a broad selection of commercially available immunoassays and evaluate the biotemporal stability of analytes across five pathophysiological domains of interest in AD, including core amyloid-β (Aβ) and tau AD biomarkers, neurodegeneration, inflammation/immune modulation, neurovascular injury, and metabolism/oxidative stress...
2018: PloS One
Kathy Keyvani, Yvonne Münster, Nirup K Kurapati, Sebastian Rubach, Andreas Schönborn, Emre Kocakavuk, Mohamed Karout, Pia Hammesfahr, Ya-Chao Wang, Dirk M Hermann, Sarah Teuber-Hanselmann, Arne Herring
Women seem to have a higher vulnerability to Alzheimer's disease (AD), but the underlying mechanisms of this sex dichotomy are not well understood. Here, we first determined the influence of sex on various aspects of Alzheimer's pathology in transgenic CRND8 mice. We demonstrate that beta-amyloid (Aβ) plaque burden starts to be more severe around P180 (moderate disease stage) in female transgenics when compared to males and that aging aggravates this sex-specific difference. Further we show that female transgenics suffer from higher levels of neurovascular dysfunction around P180, resulting in impaired Aβ peptide clearance across the blood-brain-barrier at P360...
March 5, 2018: Brain Pathology
Gaël Chételat
Over the last ten years, we have conducted research in Alzheimer's disease (AD) using multimodal neuroimaging techniques to improve diagnosis, further our understanding of the pathological mechanisms underlying the disease, and support the development of innovative non-pharmacological preventive strategies. Our works emphasized the interest of hippocampal subfield volumetry in early diagnosis and the need for further development in this field including optimization, standardization, and automatization of the techniques...
February 28, 2018: Journal of Alzheimer's Disease: JAD
Francesc Jiménez-Altayó, Judith Sànchez-Ventura, Elisabet Vila, Lydia Giménez-Llort
Cardiovascular disease resulting from oxidative stress and inflammation can exacerbate Alzheimer's disease. This brief report provides the first evidence of compromised small peripheral mesenteric resistance artery (MRA) properties in 15-month-old 3xTg-AD mice. Females showed worse physiologically relevant MRA structural (increased passive external and internal diameters, cross sectional area) and functional (increased active internal diameter) alterations suggesting sex-dependent dysfunctions. At both physiological and high intraluminal pressures, vascular alterations correlated with the anxious-like behavioral profile, in a sex-dependent manner...
February 28, 2018: Journal of Alzheimer's Disease: JAD
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