keyword
https://read.qxmd.com/read/38517332/a-tbk1-variant-causes-autophagolysosomal-and-motoneuron-pathology-without-neuroinflammation-in-mice
#21
JOURNAL ARTICLE
David Brenner, Kirsten Sieverding, Jahnavi Srinidhi, Susanne Zellner, Christopher Secker, Rüstem Yilmaz, Julia Dyckow, Shady Amr, Anna Ponomarenko, Esra Tunaboylu, Yasmin Douahem, Joana S Schlag, Lucía Rodríguez Martínez, Georg Kislinger, Cornelia Niemann, Karsten Nalbach, Wolfgang P Ruf, Jonathan Uhl, Johanna Hollenbeck, Lucas Schirmer, Alberto Catanese, Christian S Lobsiger, Karin M Danzer, Deniz Yilmazer-Hanke, Christian Münch, Philipp Koch, Axel Freischmidt, Martina Fetting, Christian Behrends, Rosanna Parlato, Jochen H Weishaupt
Heterozygous mutations in the TBK1 gene can cause amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The majority of TBK1-ALS/FTD patients carry deleterious loss-of-expression mutations, and it is still unclear which TBK1 function leads to neurodegeneration. We investigated the impact of the pathogenic TBK1 missense variant p.E696K, which does not abolish protein expression, but leads to a selective loss of TBK1 binding to the autophagy adaptor protein and TBK1 substrate optineurin. Using organelle-specific proteomics, we found that in a knock-in mouse model and human iPSC-derived motor neurons, the p...
May 6, 2024: Journal of Experimental Medicine
https://read.qxmd.com/read/38516716/the-link-between-the-early-surgery-induced-inflammatory-response-and-postoperative-cognitive-dysfunction-in-older-patients
#22
JOURNAL ARTICLE
Baukje Brattinga, Matthijs Plas, Jacoba M Spikman, Abraham Rutgers, Jacco J de Haan, Hanneke van der Wal-Huisman, Anthony R Absalom, Gertrude J Nieuwenhuijs-Moeke, Barbara C van Munster, Geertruida H de Bock, Barbara L van Leeuwen
BACKGROUND: Postoperative cognitive dysfunction (POCD) is a common complication in older patients with cancer and is associated with decreased quality of life and increased disability and mortality rates. Systemic inflammation resulting in neuroinflammation is considered important in the pathogenesis of POCD. The aim of this study was to explore the association between the early surgery-induced inflammatory response and POCD within 3 months after surgery in older cancer patients...
March 22, 2024: Journal of the American Geriatrics Society
https://read.qxmd.com/read/38515329/early-amyloid-induced-changes-in-microglia-gene-expression-in-male-app-ps1-mice
#23
JOURNAL ARTICLE
Takuya Oshima, Mandy S J Kater, Christiaan F M Huffels, Evelyn M Wesseling, Jinte Middeldorp, Elly M Hol, Mark H G Verheijen, August B Smit, Erik W G M Boddeke, Bart J L Eggen
Alzheimer's disease (AD) is a progressive neurodegenerative disease and the most common cause of dementia, characterized by deposition of extracellular amyloid-beta (Aβ) aggregates and intraneuronal hyperphosphorylated Tau. Many AD risk genes, identified in genome-wide association studies (GWAS), are expressed in microglia, the innate immune cells of the central nervous system. Specific subtypes of microglia emerged in relation to AD pathology, such as disease-associated microglia (DAMs), which increased in number with age in amyloid mouse models and in human AD cases...
March 2024: Journal of Neuroscience Research
https://read.qxmd.com/read/38515326/dual-effects-of-tgf-%C3%AE-inhibitor-in-als-inhibit-contracture-and-neurodegeneration
#24
JOURNAL ARTICLE
Do-Yeon Lee, Young Nam Kwon, Kwangkook Lee, Sang Jeong Kim, Jung-Joon Sung
As persistent elevation of transforming growth factor-β (TGF-β) promotes fibrosis of muscles and joints and accelerates disease progression in amyotrophic lateral sclerosis (ALS), we investigated whether inhibition of TGF-β would be effective against both exacerbations. The effects of TGF-β and its inhibitor on myoblasts and fibroblasts were tested in vitro and confirmed in vivo, and the dual action of a TGF-β inhibitor in ameliorating the pathogenic role of TGF-β in ALS mice was identified...
March 21, 2024: Journal of Neurochemistry
https://read.qxmd.com/read/38515139/hypochlorous-acid-derived-from-microglial-myeloperoxidase-could-mediate-high-mobility-group-box-1-release-from-neurons-to-amplify-brain-damage-in-cerebral-ischemia-reperfusion-injury
#25
JOURNAL ARTICLE
Shuang Chen, Jingrui Pan, Zhe Gong, Meiling Wu, Xiaoni Zhang, Hansen Chen, Dan Yang, Suhua Qi, Ying Peng, Jiangang Shen
Myeloperoxidase (MPO) plays critical role in the pathology of cerebral ischemia-reperfusion (I/R) injury via producing hypochlorous acid (HOCl) and inducing oxidative modification of proteins. High-mobility group box 1 (HMGB1) oxidation, particularly disulfide HMGB1 formation, facilitates the secretion and release of HMGB1 and activates neuroinflammation, aggravating cerebral I/R injury. However, the cellular sources of MPO/HOCl in ischemic brain injury are unclear yet. Whether HOCl could promote HMGB1 secretion and release remains unknown...
March 21, 2024: Journal of Neuroinflammation
https://read.qxmd.com/read/38513881/paeoniflorin-ameliorates-oxaliplatin-induced-peripheral-neuropathy-via-inhibiting-neuroinflammation-through-influence-on-gut-microbiota
#26
JOURNAL ARTICLE
Jiayue Xu, Langqing Lu, Shiqin Jiang, Zhiyan Qin, Junyuan Huang, Min Huang, Jing Jin
Oxaliplatin (OXA)-induced peripheral neuropathy (OIPN) is a severe side effect that greatly limits OXA clinical use and threatens patients' life and health. Paeoniflorin exhibits extensive anti-inflammatory and neuroprotective effects, but whether it can protect against OIPN and the underlying mechanisms remain unclear. This study aimed to investigate the effects of paeoniflorin on OIPN and probe into the underlying mechanisms. The OIPN model was established through oxaliplatin injection in rats. The ameliorative effects of paeoniflorin on OIPN was assessed by nociceptive hypersensitivities through pain behavioral methods...
March 19, 2024: European Journal of Pharmacology
https://read.qxmd.com/read/38513138/alterations-of-the-blood-brain-barrier-during-aging
#27
REVIEW
Yufan Cao, Weihai Xu, Qing Liu
The blood-brain barrier (BBB) is a complex and dynamic interface that regulates the exchange of molecules and cells between the blood and the central nervous system. It undergoes structural and functional changes during aging, which may compromise its integrity and contribute to the pathogenesis of neurodegenerative diseases. In recent years, advances in microscopy and high-throughput bioinformatics have allowed a more in-depth investigation of the aging mechanisms of BBB. This review summarizes age-related alterations of the BBB structure and function from six perspectives: endothelial cells, astrocytes, pericytes, basement membrane, microglia and perivascular macrophages, and fibroblasts, ranging from the molecular level to the human multi-system level...
March 21, 2024: Journal of Cerebral Blood Flow and Metabolism
https://read.qxmd.com/read/38509618/deletion-of-slc9a1-in-cx3cr1-cells-stimulated-microglial-subcluster-creb1-signaling-and-microglia-oligodendrocyte-crosstalk
#28
JOURNAL ARTICLE
Shanshan Song, Helena Oft, Shamseldin Metwally, Satya Paruchuri, John Bielanin, Victoria Fiesler, Chaim Sneiderman, Gary Kohanbash, Dandan Sun
Microglial Na/H exchanger-1 (NHE1) protein, encoded by Slc9a1, plays a role in white matter demyelination of ischemic stroke brains. To explore underlying mechanisms, we conducted single cell RNA-seq transcriptome analysis in conditional Slc9a1 knockout (cKO) and wild-type (WT) mouse white matter tissues at 3 days post-stroke. Compared to WT, Nhe1 cKO brains expanded a microglial subgroup with elevated transcription of white matter myelination genes including Spp1, Lgals3, Gpnmb, and Fabp5. This subgroup also exhibited more acidic pHi and significantly upregulated CREB signaling detected by ingenuity pathway analysis and flow cytometry...
March 20, 2024: Journal of Neuroinflammation
https://read.qxmd.com/read/38508536/host-single-nucleotide-polymorphisms-and-biomarkers-of-neuronal-damage-and-inflammation-in-people-living-with-hiv
#29
JOURNAL ARTICLE
Jessica Cusato, Alessandra Manca, Alice Palermiti, Jacopo Mula, Valeria Avataneo, Miriam Antonucci, Letizia Marinaro, Stefano Bonora, Mattia Trunfio, Giovanni Di Perri, Antonio D'Avolio, Andrea Calcagno
BACKGROUND: Blood brain barrier impairment is frequent in people living with HIV (PLWH), affecting the penetration of target cells and antiretrovirals into the central nervous system, through transporters (e.g. ABCB1), leading to neuroinflammation. OBJECTIVES: The aim of this study was to identify variants of genes encoding transporters able to predict neuroinflammation biomarker levels. MATERIALS AND METHODS: Cerebrospinal fluid (CSF) and plasma samples were obtained from PLWH...
March 18, 2024: International Journal of Antimicrobial Agents
https://read.qxmd.com/read/38507708/thymol-as-a-potential-neuroprotective-agent-mechanisms-efficacy-and-future-prospects
#30
REVIEW
Xinyan Peng, Xiaowen Zhang, Gaurav Sharma, Chongshan Dai
Neurodegenerative diseases pose a growing global health challenge, with limited effective therapeutic options. Mitochondrial dysfunction, oxidative stress, neuroinflammation, apoptosis, and autophagy are common underlying mechanisms in these diseases. Thymol is a phenolic monoterpene compound that has gained attention for its diverse biological properties, including antioxidant, anti-inflammatory, and immunomodulatory activities. Thymol supplementation could provide potential neuroprotection and improve cognitive deficits, depressant-like effects, learning, and memory impairments in rodents...
March 20, 2024: Journal of Agricultural and Food Chemistry
https://read.qxmd.com/read/38507417/post-treatment-with-maropitant-reduces-oxidative-stress-endoplasmic-reticulum-stress-and-neuroinflammation-on-peripheral-nerve-injury-in-rats
#31
JOURNAL ARTICLE
Raquel Vieira Niella, Janaína Maria Xavier Corrêa, João Felipe Ribeiro Dos Santos, Larissa Ferreira Lima, Claire Souza da Costa Marques, Luciano Cardoso Santos, Larissa Rodrigues Santana, Álvaro José Chávez Silva, Keilane Silva Farias, Carlos Priminho Pirovani, Juneo Freitas Silva, Mário Sérgio Lima de Lavor
OBJECTIVE: To determine the effective dose and therapeutic potential of maropitant using through expression of mediators of oxidative stress, inflammatory and of the unfolded protein response (UPR) (bio) markers on spinal cord using a model of neuropathic pain induced through chronic constriction injury (CCI) in rats. STUDY DESIGN: Randomized, blinded, prospective experimental study. ANIMALS: 98 male Wistar rats. METHODS: Rats were anesthetized with sevoflurane and after CCI, they were randomly assigned to the following groups that received: vehicle, 3, 6, 15, 30 e 50 mg/kg/24q of maropitant...
2024: PloS One
https://read.qxmd.com/read/38506634/the-abca7-v1613m-variant-reduces-a%C3%AE-generation-plaque-load-and-neuronal-damage
#32
JOURNAL ARTICLE
Claire A Butler, Adrian Mendoza Arvilla, Giedre Milinkeviciute, Celia Da Cunha, Shimako Kawauchi, Narges Rezaie, Heidi Y Liang, Dominic Javonillo, Annie Thach, Shuling Wang, Sherilyn Collins, Amber Walker, Kai-Xuan Shi, Jonathan Neumann, Angela Gomez-Arboledas, Caden M Henningfield, Lindsay A Hohsfield, Mark Mapstone, Andrea J Tenner, Frank M LaFerla, Ali Mortazavi, Grant R MacGregor, Kim N Green
BACKGROUND: Variants in ABCA7, a member of the ABC transporter superfamily, have been associated with increased risk for developing late onset Alzheimer's disease (LOAD). METHODS: CRISPR-Cas9 was used to generate an Abca7V1613M variant in mice, modeling the homologous human ABCA7V1599M variant, and extensive characterization was performed. RESULTS: Abca7V1613M microglia show differential gene expression profiles upon lipopolysaccharide challenge and increased phagocytic capacity...
March 20, 2024: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://read.qxmd.com/read/38506067/apoe4-dysregulation-incites-depressive-symptoms-and-mitochondrial-impairments-in-mice
#33
JOURNAL ARTICLE
Weifen Li, Tahir Ali, Kaiwu He, Chengyou Zheng, Ningning Li, Zhi-Jian Yu, Shupeng Li
Apolipoprotein E4 (ApoE4) is involved in the stress-response processes and is hypothesized to be a risk factor for depression by means of mitochondrial dysfunction. However, their exact roles and underlying mechanisms are largely unknown. ApoE4 transgenic mice (B6. Cg-ApoEtm1Unc Cdh18Tg( GFAP-APOE i4)1Hol /J) were subjected to stress (lipopolysaccharides, LPS) to elucidate the aetiology of ApoE4-induced depression. LPS treatment significantly aggravated depression-like behaviours, concurrent with neuroinflammation and impaired mitochondrial changes, and melatonin/Urolithin A (UA) + 5-aminoimidazole-4-carboxamide 1-β-D-ribofuranoside (AICAR) reversed these effects in ApoE4 mice...
April 2024: Journal of Cellular and Molecular Medicine
https://read.qxmd.com/read/38504697/pretreated-mscs-with-ironq-transplantation-attenuate-microglia-neuroinflammation-via-the-cgas-sting-signaling-pathway
#34
JOURNAL ARTICLE
Guoqiang Yang, Jiraporn Kantapan, Maryam Mazhar, Qiongdan Hu, Xue Bai, Yuanxia Zou, Honglian Wang, Sijin Yang, Li Wang, Nathupakorn Dechsupa
BACKGROUND: Intracerebral hemorrhage (ICH), a devastating form of stroke, is characterized by elevated morbidity and mortality rates. Neuroinflammation is a common occurrence following ICH. Mesenchymal stem cells (MSCs) have exhibited potential in treating brain diseases due to their anti-inflammatory properties. However, the therapeutic efficacy of MSCs is limited by the intense inflammatory response at the transplantation site in ICH. Hence, enhancing the function of transplanted MSCs holds considerable promise as a therapeutic strategy for ICH...
2024: Journal of Inflammation Research
https://read.qxmd.com/read/38504548/complementary-and-alternative-medicine-on-cognitive-defects-and-neuroinflammation-after-sepsis
#35
JOURNAL ARTICLE
L I Zhenxuan, Wang Xuerui, Luis Ulloa, Ayman Youssef, Bai Yunjing, X U Xiaolong, Liu Qingquan
Sepsis-associated encephalopathy (SAE) is a common manifestation of sepsis, ranging from mild confusion and delirium to severe cognitive impairment and deep coma. SAE is associated with higher mortality and long-term outcomes, particularly substantial declines in cognitive function. The mechanisms of SAE probably include neuroinflammation that is mediated by systemic inflammation and ischemic lesions in the brain, a disrupted blood-brain barrier, oxidative stress, neurotransmitter dysfunction, and severe microglial activation...
April 2024: Journal of Traditional Chinese Medicine
https://read.qxmd.com/read/38504306/unraveling-the-therapeutic-efficacy-of-resveratrol-in-alzheimer-s-disease-an-umbrella-review-of-systematic-evidence
#36
REVIEW
Ali Azargoonjahromi, Fatemeh Abutalebian
CONTEXT: Resveratrol (RV), a natural compound found in grapes, berries, and peanuts, has been extensively studied for its potential in treating Alzheimer's disease (AD). RV has shown promise in inhibiting the formation of beta-amyloid plaques (Aβ) and neurofibrillary tangles (NFTs), protecting against neuronal damage and oxidative stress, reducing inflammation, promoting neuroprotection, and improving the function of the blood-brain barrier (BBB). However, conflicting results have been reported, necessitating a comprehensive umbrella review of systematic reviews to provide an unbiased conclusion on the therapeutic effectiveness of RV in AD...
March 19, 2024: Nutrition & Metabolism
https://read.qxmd.com/read/38503399/quercetin-3-o-glc-1-3-rham-1-6-glucoside-decreases-a%C3%AE-production-inhibits-a%C3%AE-aggregation-and-neurotoxicity-and-prohibits-the-production-of-inflammatory-cytokines
#37
JOURNAL ARTICLE
Shuo Tan, Linmei Wu, Jiayi Liu, Zhaoyuan Wu, Qiang Cheng, Qiuhao Qu, Lianghao Zhu, Yizhu Yan, Hao Wu, Tie-Jun Ling, Rui-Tian Liu, Shigao Yang
Alzheimer's disease (AD) is a progressive neurodegenerative disease with the hallmark of aggregation of beta-amyloid (Aβ) into extracellular fibrillar deposition. Accumulating evidence suggests that soluble toxic Aβ oligomers exert diverse roles in neuronal cell death, oxidative stress, neuroinflammation, and the eventual pathogenesis of AD. Aβ is derived from the sequential cleavage of amyloid-β precursor protein (APP) by β-secretase (BACE1) and γ-secretase. The current effect of single targeting is not ideal for the treatment of AD...
March 17, 2024: European Journal of Pharmacology
https://read.qxmd.com/read/38501412/-resveratrol-protects-dopaminergic-neurons-in-a-mouse-model-of-parkinson-s-disease-by-regulating-the-gut-brain-axis-via-inhibiting-the-tlr4-signaling-pathway
#38
JOURNAL ARTICLE
J Gui, X Sun, S Wen, X Liu, B Qin, M Sang
OBJECTIVE: To investigate the protective effect of resveratrol on intestinal barrier in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) mouse models and its mechanism for regulating TLR4/MyD88/NF-κB signaling to protect dopaminergic neurons. METHODS: Fifty-two C57BL/6J mice were randomized into control group ( n = 12), MPTP group ( n =14), MPTP + resveratrol (30 mg/kg) group ( n =13), and MPTP + resveratrol (90 mg/kg) group ( n =13), and mouse models were established by intraperitoneal MPTP (30 mg/kg) injection for 7 days in the latter 3 groups...
February 20, 2024: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://read.qxmd.com/read/38500151/macrophages-coordinate-immune-response-to-laser-induced-injury-via-extracellular-traps
#39
JOURNAL ARTICLE
Federica M Conedera, Despina Kokona, Martin S Zinkernagel, Jens V Stein, Charles P Lin, Clemens Alt, Volker Enzmann
BACKGROUND: Retinal degeneration results from disruptions in retinal homeostasis due to injury, disease, or aging and triggers peripheral leukocyte infiltration. Effective immune responses rely on coordinated actions of resident microglia and recruited macrophages, critical for tissue remodeling and repair. However, these phagocytes also contribute to chronic inflammation in degenerated retinas, yet the precise coordination of immune response to retinal damage remains elusive. Recent investigations have demonstrated that phagocytic cells can produce extracellular traps (ETs), which are a source of self-antigens that alter the immune response, which can potentially lead to tissue injury...
March 18, 2024: Journal of Neuroinflammation
https://read.qxmd.com/read/38500108/modulation-of-hippocampal-protein-expression-by-a-brain-penetrant-biologic-tnf-%C3%AE-inhibitor-in-the-3xtg-alzheimer-s-disease-mice
#40
JOURNAL ARTICLE
Nataraj Jagadeesan, G Chuli Roules, Devaraj V Chandrashekar, Joshua Yang, Sanjana Kolluru, Rachita K Sumbria
BACKGROUND: Biologic TNF-α inhibitors (bTNFIs) can block cerebral TNF-α in Alzheimer's disease (AD) if these macromolecules can cross the blood-brain barrier (BBB). Thus, a model bTNFI, the extracellular domain of type II TNF-α receptor (TNFR), which can bind to and sequester TNF-α, was fused with a mouse transferrin receptor antibody (TfRMAb) to enable brain delivery via BBB TfR-mediated transcytosis. Previously, we found TfRMAb-TNFR to be protective in a mouse model of amyloidosis (APP/PS1) and tauopathy (PS19), and herein we investigated its effects in mice that combine both amyloidosis and tauopathy (3xTg-AD)...
March 18, 2024: Journal of Translational Medicine
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