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https://www.readbyqxmd.com/read/28342971/a-novel-dual-glp-1-gip-receptor-agonist-alleviates-cognitive-decline-by-re-sensitizing-insulin-signaling-in-the-alzheimer-icv-stz-rat-model
#1
Lijuan Shi, Zhihua Zhang, Lin Li, Christian Hölscher
Alzheimer's disease (AD) is a progressive neurodegenerative disorder, accompanied by memory loss and cognitive impairments, and there is no effective treatment for it at present. Since type 2 diabetes (T2DM) has been identified as a risk factor for AD, the incretins glucagon-like peptide 1 (GLP-1) and glucose dependent insulinotropic polypeptide (GIP), promising antidiabetic agents for the treatment of type 2 diabetes, have been tested in models of neurodegenerative disease including AD and achieved good results...
March 22, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28342781/modulation-of-neuroinflammation-the-role-and-therapeutic-potential-of-transient-receptor-potential-vanilloid-1-in-neuro-immune-axis
#2
REVIEW
Wei-Lin Kong, Yuan-Yuan Peng, Bi-Wen Peng
Transient receptor potential vanilloid type 1 channel (TRPV1), as a ligand-gated non-selective cation channel, has recently been demonstrated to have wide expression in the neuro-immune axis, where its multiple functions occur through regulation of both neuronal and non-neuronal activities. Growing evidence has suggested that TRPV1 is functionally expressed in glial cells, especially in the microglia and astrocytes. Glial cells perform immunological functions in response to pathophysiological challenges through pro-inflammatory or anti-inflammatory cytokines and chemokines in which TRPV1 is involved...
March 22, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28338241/neuroprotective-effects-of-loganin-on-mptp-induced-parkinson-s-disease-mice-neurochemistry-glial-reaction-and-autophagy-studies
#3
Yi-Da Xu, Chun Cui, Meng-Fei Sun, Ying-Li Zhu, Min Chu, Yun-Wei Shi, Stanley Li Lin, Xu-Sheng Yang, Yan-Qin Shen
Parkinson's disease (PD) is a progressive neurodegenerative disease, involving resting tremor and bradykinesia, for which no recognized therapies or drugs are available to halt or slow progression. In recent years, natural botanic products have been considered relatively safe, with limited side effects, and are expected to become an important source for clinical mediation of PD in the future. Our study focuses on the ability of loganin, a compound derived from fruits of cornus, to mediate neuroprotection in a mouse model of PD...
March 24, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28337124/interleukin-4-protects-dopaminergic-neurons-in-vitro-but-is-dispensable-for-mptp-induced-neurodegeneration-in-vivo
#4
Laura Hühner, Jennifer Rilka, Ralf Gilsbach, Xiaolai Zhou, Venissa Machado, Björn Spittau
Microglia are involved in physiological as well as neuropathological processes in the central nervous system (CNS). Their functional states are often referred to as M1-like and M2-like activation, and are believed to contribute to neuroinflammation-mediated neurodegeneration or neuroprotection, respectively. Parkinson's disease (PD) is one the most common neurodegenerative disease and is characterized by the progressive loss of midbrain dopaminergic (mDA) neurons in the substantia nigra resulting in bradykinesia, tremor, and rigidity...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28336525/extracellular-tdp-43-aggregates-target-mapk-mak-mrk-overlapping-kinase-mok-and-trigger-caspase-3-il-18-signaling-in-microglia
#5
María M Leal-Lasarte, Jaime M Franco, Adahir Labrador-Garrido, David Pozo, Cintia Roodveldt
Dysregulated microglial responses are central in neurodegenerative proteinopathies, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar disease (FTLD). Pathologic TDP-43, which is typically found in intracellular inclusions, is a misfolding protein with emerging roles in ALS and FTLD. Recently, TDP-43 species have been found in extracellular fluids of patients; however, the overall implications of TDP-43-mediated signaling linked to neuroinflammation are poorly understood. Our work-the first, to our knowledge, to focus on innate immunity responses to TDP-43 aggregates-shows that such species are internalized by microglia and cause abnormal mobilization of endogenous TDP-43...
March 23, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28322157/diabetes-related-neurological-implications-and-pharmacogenomics
#6
Rojas Carranza Camilo Andrés, Bustos Cruz Rosa Helena, Pino Pinzón Carmen Juliana, Ariza Marquez Yeimy Viviana, Gómez Bello Rosa Margarita, Cañadas Garre Marisa
Diabetes mellitus (DM) is the most commonly occurring cause of neuropathy around the world and is beginning to grow in countries where there is a risk of obesity. DM Type II, (T2DM) is a common age-related disease and is a major health concern, particularly in developed countries in Europe where the population is aging. T2DM is a chronic disease which is characterised by hyperglycemia, hyperinsulinemia and insulin resistance, together with the body's inability to use glucose as energy. Such metabolic disorder produces a chronic inflammatory state, as well as changes in lipid metabolism leading to hypertriglyceridemia, thereby producing chronic deterioration of the organs and premature morbidity and mortality...
March 17, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28320965/deficiency-of-a-sulfotransferase-for-sialic-acid-modified-glycans-mitigates-alzheimer-s-pathology
#7
Zui Zhang, Yoshiko Takeda-Uchimura, Tahmina Foyez, Shiori Ohtake-Niimi, Narentuya, Hiroyasu Akatsu, Kazuchika Nishitsuji, Makoto Michikawa, Tony Wyss-Coray, Kenji Kadomatsu, Kenji Uchimura
We previously showed that microglial keratan sulfate (KS) was induced in amyotrophic lateral sclerosis. However, the functional roles of the glycan and its synthetic enzyme in neurodegenerative diseases, such as Alzheimer's disease (AD), a progressive disorder, are unclear. In our study, KS modified with sialic acids having a molecular mass of 125-220 kDa and the carbohydrate sulfotransferase GlcNAc6ST1 were up-regulated in the brains of two transgenic mouse models (J20 and Tg2576) and the brains of patients with AD...
March 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28318352/the-role-of-nlrp3-casp1-in-inflammasome-mediated-neuroinflammation-and-autophagy-dysfunction-in-manganese-induced-hippocampal-dependent-impairment-of-learning-and-memory-ability
#8
Diya Wang, Jianbin Zhang, Wenkai Jiang, Zipeng Cao, Fang Zhao, Tongjian Cai, Michael Aschner, Wenjing Luo
Central nervous system (CNS) inflammation and autophagy dysfunction are known to be involved in the pathology of neurodegenerative diseases. Manganese (Mn), a neurotoxic metal, has the potential to induce microglia-mediated neuroinflammation as well as autophagy dysfunction. NLRP3 (NLR family, pyrin domain containing 3)- CASP1 (caspase 1) inflammasome-mediated neuroinflammation in microglia has specific relevance to neurological diseases. However, the mechanism driving these phenomena remains poorly understood...
February 27, 2017: Autophagy
https://www.readbyqxmd.com/read/28303091/divergent-neuroinflammatory-regulation-of-microglial-trem-expression-and-involvement-of-nf-%C3%AE%C2%BAb
#9
Rosie Owens, Kathleen Grabert, Claire L Davies, Alessio Alfieri, Jack P Antel, Luke M Healy, Barry W McColl
The triggering receptor expressed on myeloid cells (TREM) family of proteins are cell surface receptors with important roles in regulation of myeloid cell inflammatory activity. In the central nervous system, TREM2 is implicated in further roles in microglial homeostasis, neuroinflammation and neurodegeneration. Different TREM receptors appear to have contrasting roles in controlling myeloid immune activity therefore the relative and co-ordinated regulation of their expression is important to understand but is currently poorly understood...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28302159/a-data-driven-approach-links-microglia-to-pathology-and-prognosis-in-amyotrophic-lateral-sclerosis
#10
Johnathan Cooper-Knock, Claire Green, Gabriel Altschuler, Wenbin Wei, Joanna J Bury, Paul R Heath, Matthew Wyles, Catherine Gelsthorpe, J Robin Highley, Alejandro Lorente-Pons, Tim Beck, Kathryn Doyle, Karel Otero, Bryan Traynor, Janine Kirby, Pamela J Shaw, Winston Hide
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease that lacks a predictive and broadly applicable biomarker. Continued focus on mutation-specific upstream mechanisms has yet to predict disease progression in the clinic. Utilising cellular pathology common to the majority of ALS patients, we implemented an objective transcriptome-driven approach to develop noninvasive prognostic biomarkers for disease progression. Genes expressed in laser captured motor neurons in direct correlation (Spearman rank correlation, p < 0...
March 16, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28300826/astrocyte-hepcidin-is-a-key-factor-in-lps-induced-neuronal-apoptosis
#11
Lin-Hao You, Cai-Zhen Yan, Bing-Jie Zheng, Yun-Zhe Ci, Shi-Yang Chang, Peng Yu, Guo-Fen Gao, Hai-Yan Li, Tian-Yu Dong, Yan-Zhong Chang
Inflammatory responses involving microglia and astrocytes contribute to the pathogenesis of neurodegenerative diseases (NDs). In addition, inflammation is tightly linked to iron metabolism dysregulation. However, it is not clear whether the brain inflammation-induced iron metabolism dysregulation contributes to the NDs pathogenesis. Herein, we demonstrate that the expression of the systemic iron regulatory hormone, hepcidin, is induced by lipopolysaccharide (LPS) through the IL-6/STAT3 pathway in the cortex and hippocampus...
March 16, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28300326/hur-promotes-the-molecular-signature-and-phenotype-of-activated-microglia-implications-for-amyotrophic-lateral-sclerosis-and-other-neurodegenerative-diseases
#12
Prachi Matsye, Lei Zheng, Ying Si, Soojin Kim, Wenyi Luo, David K Crossman, Preston E Bratcher, Peter H King
In neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), chronic activation of microglia contributes to disease progression. Activated microglia produce cytokines, chemokines, and other factors that normally serve to clear infection or damaged tissue either directly or through the recruitment of other immune cells. The molecular program driving this phenotype is classically linked to the transcription factor NF-κB and characterized by the upregulation of proinflammatory factors such as IL-1β, TNF-α, and IL-6...
March 16, 2017: Glia
https://www.readbyqxmd.com/read/28292831/reduction-of-ether-type-glycerophospholipids-plasmalogens-by-nf-%C3%AE%C2%BAb-signal-leading-to-microglial-activation
#13
Md Shamim Hossain, Yuichi Abe, Fatma Ali, Mohammed Youssef, Masanori Honsho, Yukio Fujiki, Toshihiko Katafuchi
Neuroinflammation characterized by activation of glial cells is observed in various neurodegenerative diseases including Alzheimer's disease (AD). Although the reduction of ether-type glycerophospholipids, plasmalogens (Pls), in the brain is reported in AD patients, the mechanism of the reduction and its impact on neuroinflammation remained elusive. In the present study, we found for the first time that various inflammatory stimuli reduced the Pls levels in the murine glial cells via NF-κB activation which then down-regulated a Pls synthesizing enzyme, glycerone phosphate O-acyltransferase (Gnpat) through the increased c-Myc recruitment onto the Gnpat promoter...
March 14, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28292183/n-docosahexaenoyl-dopamine-an-endocannabinoid-like-conjugate-of-dopamine-and-the-n-3-fatty-acid-docosahexaenoic-acid-attenuates-lipopolysaccharide-induced-activation-of-microglia-and-macrophages-via-cox-2
#14
Ya Wang, Pierluigi Plastina, Jean-Paul Vincken, Renate Jansen, Michiel Balvers, Jean Paul Ten Klooster, Harry Gruppen, Renger Witkamp, Jocelijn Meijerink
Several studies indicate that the n-3 long-chain polyunsaturated fatty acid docosahexaenoic acid (DHA) contributes to an attenuated inflammatory status in the development of neurodegenerative disorders, such as Alzheimer's and Parkinson's disease. To explain these effects, different mechanisms are being proposed, including those involving endocannabinoids and related signaling molecules. Many of these compounds belong to the fatty acid amides, conjugates of fatty acids with biogenic amines. Conjugates of DHA with ethanolamine or serotonin have previously been shown to possess anti-inflammatory and potentially neuroprotective properties...
March 15, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28288940/anti-inflammatory-mechanism-of-lonchocarpine-in-lps-or-poly-i-c-induced-neuroinflammation
#15
Yeon-Hui Jeong, Jin-Sun Park, Dong-Hyun Kim, Jihee Lee Kang, Hee-Sun Kim
Neuroinflammation plays an important role in the progression of various neurodegenerative diseases. In this study, we investigated the anti-inflammatory effects of lonchocarpine, a natural compound isolated from Abrus precatorius, under in vitro and in vivo neuroinflammatory conditions induced by challenge with lipopolysaccharide (LPS)- or polyinosinic-polycytidylic acid (poly(I:C)). Lonchocarpine suppressed the expression of iNOS and proinflammatory cytokines in LPS or poly(I:C)-stimulated BV2 microglial cells...
March 10, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28286294/specific-suppression-of-microgliosis-cannot-circumvent-the-severe-neuropathology-in-peroxisomal-%C3%AE-oxidation-deficient-mice
#16
L Beckers, S Stroobants, S Verheijden, B West, R D'Hooge, M Baes
An important hallmark of various neurodegenerative disorders is the proliferation and activation of microglial cells, the resident immune cells of the central nervous system (CNS). Mice that lack multifunctional protein-2 (MFP2), the key enzyme in peroxisomal β-oxidation, develop excessive microgliosis that positively correlates with behavioral deficits whereas no neuronal loss occurs. However, the precise contribution of neuroinflammation to the fatal neuropathology of MFP2 deficiency remains largely unknown...
March 7, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28285347/endothelin-1-induces-degeneration-of-cultured-motor-neurons-through-a-mechanism-mediated-by-nitric-oxide-and-pi3k-akt-pathway
#17
S D'Antoni, E Ranno, M Spatuzza, S Cavallaro, M V Catania
Endothelin-1 (ET-1) is a vasoactive peptide produced by activated astrocytes and microglia and is implicated in initiating and sustaining reactive gliosis in neurodegenerative diseases. We have previously suggested that ET-1 can play a role in the pathophysiology of amyotrophic lateral sclerosis (ALS). Indeed, we reported that this peptide is abundantly expressed in reactive astrocytes in the spinal cord of SOD1-G93A mice and ALS patients and exerts a toxic effect on motor neurons (MNs) in an in vitro model of mixed spinal cord cultures enriched with reactive astrocytes...
March 11, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28284334/voluntary-wheel-running-differentially-affects-disease-outcomes-in-male-and-female-mice-with-experimental-autoimmune-encephalomyelitis
#18
Katherine A Mifflin, Emma Frieser, Curtis Benson, Glen Baker, Bradley J Kerr
Multiple sclerosis (MS) is an inflammatory neurodegenerative disease of the central nervous system. The primary symptoms of MS include the loss of sensory and motor function. Exercise has been shown to modulate disease parameters in experimental autoimmune encephalomyelitis (EAE), a mouse model of MS, by reducing immune cell infiltration and oxidative stress. However, these initial studies were carried out exclusively in female mice. The present study compared the effects of daily voluntary wheel running on several disease parameters in male and female mice with EAE...
April 15, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28282924/autophagy-and-microglia-novel-partners-in-neurodegeneration-and-aging
#19
REVIEW
Ainhoa Plaza-Zabala, Virginia Sierra-Torre, Amanda Sierra
Autophagy is emerging as a core regulator of Central Nervous System (CNS) aging and neurodegeneration. In the brain, it has mostly been studied in neurons, where the delivery of toxic molecules and organelles to the lysosome by autophagy is crucial for neuronal health and survival. However, we propose that the (dys)regulation of autophagy in microglia also affects innate immune functions such as phagocytosis and inflammation, which in turn contribute to the pathophysiology of aging and neurodegenerative diseases...
March 9, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28277939/potassium-channel-expression-and-function-in-microglia-plasticity-and-possible-species-variations
#20
Hai M Nguyen, Linda V Blomster, Palle Christophersen, Heike Wulff
Potassium channels play important roles in microglia functions and thus constitute potential targets for the treatment of neurodegenerative diseases like Alzheimer, Parkinson and stroke. However, uncertainty still prevails as to which potassium channels are expressed and at what levels in different species, how the expression pattern changes upon activation with M1 or M2 polarizing stimuli compared with more complex exposure paradigms, and - most importantly - how these findings relate to the in vivo situation...
March 1, 2017: Channels
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