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Alzheimer inflammation

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https://www.readbyqxmd.com/read/29454265/supplementation-of-lycopene-attenuates-lipopolysaccharide-induced-amyloidogenesis-and-cognitive-impairments-via-mediating-neuroinflammation-and-oxidative-stress
#1
Jia Wang, Lixia Li, Zhuo Wang, Yifan Cui, Xintong Tan, Tian Yuan, Qian Liu, Zhigang Liu, Xuebo Liu
Neuroinflammation is documented to be the major culprit of Alzheimer's disease. Lycopene (LYC), a fat soluble carotenoid, exhibits neuroprotective function in several neurodegenerative disorders. However, the effects of LYC to countering systemic inflammation-induced amyloidogenesis and memory deficiency remain to be elucidated. In current study, 3-month-old male C57BL/6J mice were treated with 0.03% LYC (w/w, mixed into normal chow) for 5 weeks. The mice were then treated by intraperitoneal injection of LPS (0...
February 2, 2018: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/29454102/inflammation-as-a-possible-link-between-dyslipidemia-and-alzheimer-s-disease
#2
REVIEW
Bruno Cabral de Lima Oliveira, Paula Maria Quaglio Bellozi, Helton José Reis, Antônio Carlos Pinheiro de Oliveira
Alzheimer's disease (AD) is the leading cause of dementia worldwide. This pathological condition is characterized not only by Aβ and tau accumulation in the central nervous system (CNS), but also by inflammation, processes that can lead to neurodegeneration. Besides that, other factors may contribute to the development of AD, such as dyslipidemias. Changes in lipid levels can either influence the activity of enzymes related to the protein deposition that occurs in this pathological condition, or enhance the peripheral and CNS immune responses...
February 14, 2018: Neuroscience
https://www.readbyqxmd.com/read/29452983/orchestration-of-nlrp3-inflammasome-activation-by-ion-fluxes
#3
REVIEW
Tao Gong, Yanqing Yang, Tengchuan Jin, Wei Jiang, Rongbin Zhou
The assembly of the NLRP3 inflammasome can promote the release of IL-1β/IL-18 and initiate pyroptosis. Accordingly, the dysregulation of NLRP3 inflammasome activation is involved in a variety of human diseases, including gout, diabetes, and Alzheimer's disease. NLRP3 can sense a variety of structurally unrelated pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs) to trigger inflammation, but the unifying mechanism of NLRP3 activation is still poorly understood. Increasing evidence suggests that intracellular ions, such as K + , Ca 2+ , and Cl - , have a significant role in NLRP3 inflammasome activation...
February 13, 2018: Trends in Immunology
https://www.readbyqxmd.com/read/29448961/nuclear-receptor-agonist-driven-modification-of-inflammation-and-amyloid-pathology-enhances-and-sustains-cognitive-improvements-in-a-mouse-model-of-alzheimer-s-disease
#4
Brad T Casali, Erin G Reed-Geaghan, Gary E Landreth
BACKGROUND: Alzheimer's disease (AD) is a highly prevalent neurodegenerative disorder characterized by pathological hallmarks of beta-amyloid plaque deposits, tau pathology, inflammation, and cognitive decline. Treatment remains a clinical obstacle due to lack of effective therapeutics. Agonists targeting nuclear receptors, such as bexarotene, reversed cognitive deficits regardless of treatment duration and age in murine models of AD. While bexarotene demonstrated marked efficacy in decreasing plaque levels following short-term treatment, prolonged treatment did not modulate plaque burden...
February 15, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29447051/targeting-crosstalk-between-nuclear-factor-erythroid-derived-2-like-2-and-nuclear-factor-kappa-beta-pathway-by-nrf2-activator-dimethyl-fumarate-in-epileptogenesis
#5
Neha Singh, Sheekha Vijayanti, Lekha Saha
Epilepsy is a complex, chronic neurological disorder characterized by increased and abnormal synchronization of neuronal electrical activity, which is manifested as seizures. It is associated with many comorbid conditions such as depression, anxiety, sleep disorder, psychiatric disorder etc. which consequently causes higher mortality rate. The understanding of its cellular and molecular mechanism is partial, because of which it remains an ongoing health problem, despite the increasing availability of newer antiepileptic drugs...
February 15, 2018: International Journal of Neuroscience
https://www.readbyqxmd.com/read/29439357/dale-schenk-one-year-anniversary-fighting-to-preserve-the-memories
#6
Cassia Overk, Eliezer Masliah
 It has been a year since we lost Dale Schenk on September 30, 2016. Dale's visionary work resulted in the remarkable discovery in 1999 that an experimental amyloid-β (Aβ) vaccine reduced the neurodegeneration in a transgenic model of Alzheimer's disease (AD). Following Dale's seminal work, several active and passive immunotherapies have since been developed and tested in the clinic for AD, Parkinson's disease (PD), and other neurodegenerative disorders. Here we provide a brief overview of the current state of development of immunotherapy for AD, PD, and other neurodegenerative disorders in the context of this anniversary...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29439331/cerebrospinal-fluid-and-plasma-levels-of-inflammation-differentially-relate-to-cns-markers-of-alzheimer-s-disease-pathology-and-neuronal-damage
#7
Brianne M Bettcher, Sterling C Johnson, Ryan Fitch, Kaitlin B Casaletto, Kate S Heffernan, Sanjay Asthana, Henrik Zetterberg, Kaj Blennow, Cynthia M Carlsson, John Neuhaus, Barbara B Bendlin, Joel H Kramer
Inflammatory markers have been shown to predict neurocognitive outcomes in aging adults; however, the degree to which peripheral markers mirror the central nervous system remains unknown. We investigated the association between plasma and cerebrospinal fluid (CSF) markers of inflammation, and explored whether these markers independently predict CSF indicators of Alzheimer's disease (AD) pathology or neuronal damage. Plasma and CSF samples were analyzed for inflammatory markers in a cohort of asymptomatic older adults (n = 173)...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29434537/how-can-a-ketogenic-diet-improve-motor-function
#8
REVIEW
Charlotte Veyrat-Durebex, Pascal Reynier, Vincent Procaccio, Rudolf Hergesheimer, Philippe Corcia, Christian R Andres, Hélène Blasco
A ketogenic diet (KD) is a normocaloric diet composed by high fat (80-90%), low carbohydrate, and low protein consumption that induces fasting-like effects. KD increases ketone body (KBs) production and its concentration in the blood, providing the brain an alternative energy supply that enhances oxidative mitochondrial metabolism. In addition to its profound impact on neuro-metabolism and bioenergetics, the neuroprotective effect of specific polyunsaturated fatty acids and KBs involves pleiotropic mechanisms, such as the modulation of neuronal membrane excitability, inflammation, or reactive oxygen species production...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29432676/genistein-a-dual-inhibitor-of-both-a%C3%AE-and-hiapp-peptides
#9
Baiping Ren, Yonglan Liu, Yanxian Zhang, Yongqing Cai, Xiong Gong, Yung Chang, Lijian Xu, Jie Zheng
Abnormal misfolding and aggregation of amyloid peptides into amyloid fibrils are a common and critical pathological event in many neurodegenerative diseases. Most of inhibitors or drugs have been developed to prevent amyloid aggregation of a specific peptide, exhibiting sequence-dependent inhibition mechanisms. It is more challenging to develop or discover inhibitors capable of preventing the aggregation of two or more different amyloid peptides. Genistein, a major phytoestrogen in soybean, has been widely used as anti-inflammation and cerebrovascular drugs due to their anti-oxidation and anti-acetylcholinesterase effects...
February 12, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29428983/low-grade-systemic-inflammation-is-associated-with-functional-disability-in-elderly-people-affected-by-dementia
#10
Carlo Cervellati, Alessandro Trentini, Cristina Bosi, Giuseppe Valacchi, Mario Luca Morieri, Amedeo Zurlo, Gloria Brombo, Angelina Passaro, Giovanni Zuliani
The decline in basic and instrumental activities of daily living (BADLs and IADLs, respectively) is a well-established clinical hallmark of dementia. Growing evidence has shown that systemic subclinical inflammation may be related to functional impairment. We evaluated the possible association between low-grade systemic inflammation and functional disability in older individuals affected by dementia. We explored the association between high-sensitivity C-reactive protein (hs-CRP) levels and BADLs/IADLs in older individuals affected by late onset Alzheimer's disease (LOAD; n 110), "mixed" dementia (n 135), or mild cognitive impairment (MCI; n 258), and compared them with 75 normal Controls...
February 10, 2018: GeroScience
https://www.readbyqxmd.com/read/29428410/fragment-growing-guided-design-of-keap1-nrf2-protein-protein-interaction-inhibitors-for-targeting-myocarditis
#11
Ning Meng, Hua Tang, Hao Zhang, Chengshi Jiang, Li Su, Xiao Min, Wannian Zhang, Hua Zhang, Zhenyuan Miao, Wen Zhang, Chunlin Zhuang
Small-molecule inhibitors that block the Keap1-Nrf2 protein-protein interactions are being intensely pursued as a new therapeutic strategy for oxidative stress-related diseases, such as cancer, diabetes, Alzheimer's disease, arteriosclerosis, inflammation and myocarditis. However, there are not enough studies on antioxidant treatments using small molecules in myocarditis. We herein provided a series of novel hydronaphthoquinones as the Keap1-Nrf2 interaction inhibitors targeting LPS-induced myocarditis both in vitro and in vivo...
February 8, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29423193/alzheimer-s-disease-hypothesis-and-related-therapies
#12
REVIEW
Xiaoguang Du, Xinyi Wang, Meiyu Geng
Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common cause for dementia. There are many hypotheses about AD, including abnormal deposit of amyloid β (Aβ) protein in the extracellular spaces of neurons, formation of twisted fibers of tau proteins inside neurons, cholinergic neuron damage, inflammation, oxidative stress, etc., and many anti-AD drugs based on these hypotheses have been developed. In this review, we will discuss the existing and emerging hypothesis and related therapies...
2018: Translational Neurodegeneration
https://www.readbyqxmd.com/read/29420357/acetyl-cholinesterase-inhibitors-and-cell-derived-peripheral-inflammatory-cytokines-in-early-stages-of-alzheimer-s-disease
#13
Nikolaos Kokras, Evangelia Stamouli, Ioannis Sotiropoulos, Everina A Katirtzoglou, Kostas T Siarkos, Georgia Dalagiorgou, Krystallenia I Alexandraki, Stavroula Coulocheri, Christina Piperi, Antonios M Politis
BACKGROUND: Clinical and preclinical studies firmly support the involvement of the inflammation in the pathogenesis of Alzheimer's disease (AD). Despite acetylcholinesterase inhibitors (AChEI) being widely used in AD patients, there is no conclusive evidence about their impact on the inflammatory response. METHODS: This study investigates peripheral proinflammatory cytokines (interferon gamma [IFN-γ], tumor necrosis factor alpha [TNF-α], and interleukins 1β [IL-1β] and 6 [IL-6]) by firstly comparing peripheral blood mononuclear cell (PBMC)-derived secretion in drug-naïve and AChEI-treated AD patients versus healthy controls...
February 7, 2018: Journal of Clinical Psychopharmacology
https://www.readbyqxmd.com/read/29420166/curcumin-mediated-regulation-of-intestinal-barrier-function-the-mechanism-underlying-its-beneficial-effects
#14
Siddhartha S Ghosh, Hongliang He, Jing Wang, Todd W Gehr, Shobha Ghosh
Curcumin has anti-inflammatory, anti-oxidant and anti-proliferative properties established largely by in vitro studies. Accordingly, oral administration of curcumin beneficially modulates many diseases including diabetes, fatty-liver disease, atherosclerosis, arthritis, cancer and neurological disorders such as depression, Alzheimer's or Parkinson's disease. However, limited bioavailability and inability to detect curcumin in circulation or target tissues has hindered the validation of a causal role. We established curcumin-mediated decrease in the release of gut bacteria-derived lipopolysaccharide (LPS) into circulation by maintaining the integrity of the intestinal barrier function as the mechanism underlying the attenuation of metabolic diseases (diabetes, atherosclerosis, kidney disease) by curcumin supplementation precluding the need for curcumin absorption...
January 8, 2018: Tissue Barriers
https://www.readbyqxmd.com/read/29413525/synaptotoxic-signaling-by-amyloid-beta-oligomers-in-alzheimer-s-disease-through-prion-protein-and-mglur5
#15
A Harrison Brody, Stephen M Strittmatter
Alzheimer's disease (AD) represents an impending global health crisis, yet the complexity of AD pathophysiology has so far precluded the development of any interventions to successfully slow or halt AD progression. It is clear that accumulation of Amyloid-beta (Aβ) peptide triggers progressive synapse loss to cause AD symptoms. Once initiated by Aβ, disease progression is complicated and accelerated by inflammation and by tau pathology. The recognition that Aβ peptide assumes multiple distinct states and that soluble oligomeric species (Aβo) are critical for synaptic damage is central to molecular understanding of AD...
2018: Advances in Pharmacology
https://www.readbyqxmd.com/read/29413519/imaging-translocator-protein-as-a-biomarker-of-neuroinflammation-in-dementia
#16
William C Kreisl, Ioline D Henter, Robert B Innis
Neuroinflammation has long been considered a potential contributor to neurodegenerative disorders that result in dementia. Accumulation of abnormal protein aggregates in Alzheimer's disease, frontotemporal dementia, and dementia with Lewy bodies is associated with the activation of microglia and astrocytes into proinflammatory states, and chronic low-level activation of glial cells likely contributes to the pathological changes observed in these and other neurodegenerative diseases. The 18kDa translocator protein (TSPO) is a key biomarker for measuring inflammation in the brain via positron emission tomography (PET)...
2018: Advances in Pharmacology
https://www.readbyqxmd.com/read/29411111/functional-morphology-of-the-blood-brain-barrier-in-health-and-disease
#17
REVIEW
Stefan Liebner, Rick M Dijkhuizen, Yvonne Reiss, Karl H Plate, Dritan Agalliu, Gabriela Constantin
The adult quiescent blood-brain barrier (BBB), a structure organised by endothelial cells through interactions with pericytes, astrocytes, neurons and microglia in the neurovascular unit, is highly regulated but fragile at the same time. In the past decade, there has been considerable progress in understanding not only the molecular pathways involved in BBB development, but also BBB breakdown in neurological diseases. Specifically, the Wnt/β-catenin, retinoic acid and sonic hedgehog pathways moved into the focus of BBB research...
February 6, 2018: Acta Neuropathologica
https://www.readbyqxmd.com/read/29405769/thymoquinone-alleviates-the-experimentally-induced-alzheimer-s-disease-inflammation-by-modulation-of-tlrs-signaling
#18
Y S Abulfadl, N N El-Maraghy, Aa Eissa Ahmed, S Nofal, Y Abdel-Mottaleb, O A Badary
Alzheimer's disease (AD) is characterized by a robust inflammatory response elicited by the accumulation and deposition of amyloid-β (Aβ) within the brain. Aβ induces detrimental inflammatory responses through toll-like receptors (TLRs) signaling pathway. Thymoquinone (TQ), the main active constituent of Nigella sativa oil, has been reported by several previous studies for its potent anti-inflammatory effect. The aim of this study is to elucidate the effect of TQ in improving learning and memory, using a rat model of AD induced by a combination of aluminum chloride (AlCl 3 ) and d-galactose (d-Gal)...
January 1, 2018: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/29403551/pterostilbene-protects-against-acute-renal-ischemia-reperfusion-injury-and-inhibits-oxidative-stress-inducible-nitric-oxide-synthase-expression-and-inflammation-in-rats-via-the-toll-like-receptor-4-nuclear-factor-%C3%AE%C2%BAb-signaling-pathway
#19
Dan Gao, Sanhui Jing, Qian Zhang, Ge Wu
Previous studies have demonstrated that pterostilbene (Pter) prevents oxidative stress, suppresses cell growth and exhibits anti-fungal and anti-inflammatory effects. Pter is used to treat a number of clinical diseases, including Alzheimer's disease, various malignancies and hypercholesteremia. The aim of the present study was to investigate whether Pter protects against acute renal ischemia reperfusion injury (IRI) and inhibits oxidative stress, inducible nitric oxide synthase (iNOS) expression and inflammation in rats...
January 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29402504/novel-dual-glp-1-gip-receptor-agonists-show-neuroprotective-effects-in-alzheimer-s-and-parkinson-s-disease-models
#20
REVIEW
Christian Hölscher
Type 2 diabetes is a risk factor for several chronic neurodegenerative disorders such as Alzheimer's or Parkinson's disease. The link appears to be insulin de-sensitisation in the brain. Insulin is an important neuroprotective growth factor. GLP-1 and GIP are growth factors that re-sensitise insulin and GLP-1 mimetics are used in the clinic to treat diabetes. GLP-1 and GIP mimetics initially designed to treat diabetes show good protective effects in animal models of Alzheimer's and Parkinson's disease. Based on these results, several clinical trials have shown first encouraging effects in patients with Alzheimer's or Parkinson' disease...
January 31, 2018: Neuropharmacology
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