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Mas receptor activation facilitates innate hematoma resolution and neurological recovery after hemorrhagic stroke in mice J. Neuroinflammation (IF 9.3) Pub Date : 2024-04-24 Xiangyang Deng, Junwei Ren, Kezhu Chen, Jin Zhang, Quan Zhang, Jun Zeng, Tianwen Li, Qisheng Tang, Jian Lin, Jianhong Zhu
Intracerebral hemorrhage (ICH) is a devastating neurological disease causing severe sensorimotor dysfunction and cognitive decline, yet there is no effective treatment strategy to alleviate outcomes of these patients. The Mas axis-mediated neuroprotection is involved in the pathology of various neurological diseases, however, the role of the Mas receptor in the setting of ICH remains to be elucidated
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Pathological high intraocular pressure induces glial cell reactive proliferation contributing to neuroinflammation of the blood-retinal barrier via the NOX2/ET-1 axis-controlled ERK1/2 pathway J. Neuroinflammation (IF 9.3) Pub Date : 2024-04-22 Xin Shi, Panpan Li, Marc Herb, Hanhan Liu, Maoren Wang, Xiaosha Wang, Yuan Feng, Tim van Beers, Ning Xia, Huige Li, Verena Prokosch
NADPH oxidase (NOX), a primary source of endothelial reactive oxygen species (ROS), is considered a key event in disrupting the integrity of the blood-retinal barrier. Abnormalities in neurovascular-coupled immune signaling herald the loss of ganglion cells in glaucoma. Persistent microglia-driven inflammation and cellular innate immune system dysregulation often lead to deteriorating retinal degeneration
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Itaconate alleviates anesthesia/surgery-induced cognitive impairment by activating a Nrf2-dependent anti-neuroinflammation and neurogenesis via gut-brain axis J. Neuroinflammation (IF 9.3) Pub Date : 2024-04-22 Xiangyi Kong, Wenyuan Lyu, Xiaojie Lin, Chunlong Lin, Hao Feng, Lin Xu, Kaiyue Shan, Penghui Wei, Jianjun Li
Postoperative cognitive dysfunction (POCD) is a common neurological complication of anesthesia and surgery in aging individuals. Neuroinflammation has been identified as a hallmark of POCD. However, safe and effective treatments of POCD are still lacking. Itaconate is an immunoregulatory metabolite derived from the tricarboxylic acid cycle that exerts anti-inflammatory effects by activating the nuclear
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CSF1R antagonism results in increased supraspinal infiltration in EAE J. Neuroinflammation (IF 9.3) Pub Date : 2024-04-20 Marilyn Wang, Sofia E. Caryotakis, Glendalyn G. Smith, Alan V. Nguyen, David E. Pleasure, Athena M. Soulika
Colony stimulating factor 1 receptor (CSF1R) signaling is crucial for the maintenance and function of various myeloid subsets. CSF1R antagonism was previously shown to mitigate clinical severity in experimental autoimmune encephalomyelitis (EAE). The associated mechanisms are still not well delineated. To assess the effect of CSF1R signaling, we employed the CSF1R antagonist PLX5622 formulated in chow
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Targeting brain-peripheral immune responses for secondary brain injury after ischemic and hemorrhagic stroke J. Neuroinflammation (IF 9.3) Pub Date : 2024-04-18 Mingxu Duan, Ya Xu, Yuanshu Li, Hua Feng, Yujie Chen
The notion that the central nervous system is an immunologically immune-exempt organ has changed over the past two decades, with increasing evidence of strong links and interactions between the central nervous system and the peripheral immune system, both in the healthy state and after ischemic and hemorrhagic stroke. Although primary injury after stroke is certainly important, the limited therapeutic
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Microbiota-derived acetate attenuates neuroinflammation in rostral ventrolateral medulla of spontaneously hypertensive rats J. Neuroinflammation (IF 9.3) Pub Date : 2024-04-18 Xiaopeng Yin, Changhao Duan, Lin Zhang, Yufang Zhu, Yueyao Qiu, Kaiyi Shi, Sen Wang, Xiaoguang Zhang, Huaxing Zhang, Yinchao Hao, Fang Yuan, Yanming Tian
Increased neuroinflammation in brain regions regulating sympathetic nerves is associated with hypertension. Emerging evidence from both human and animal studies suggests a link between hypertension and gut microbiota, as well as microbiota-derived metabolites short-chain fatty acids (SCFAs). However, the precise mechanisms underlying this gut-brain axis remain unclear. The levels of microbiota-derived
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IgM anti-GM2 antibodies in patients with multifocal motor neuropathy target Schwann cells and are associated with early onset J. Neuroinflammation (IF 9.3) Pub Date : 2024-04-17 Kevin Budding, Jeroen W. Bos, Kim Dijkxhoorn, Elisabeth de Zeeuw, Lauri M. Bloemenkamp, Eva M. Zekveld, Ewout J.N. Groen, Bart C. Jacobs, Ruth Huizinga, H. Stephan Goedee, Elisabeth A. Cats, Jeanette H.W. Leusen, Leonard H. van den Berg, C. Erik Hack, W. Ludo van der Pol
Multifocal motor neuropathy (MMN) is a rare, chronic immune-mediated polyneuropathy characterized by asymmetric distal limb weakness. An important feature of MMN is the presence of IgM antibodies against gangliosides, in particular GM1 and less often GM2. Antibodies against GM1 bind to motor neurons (MNs) and cause damage through complement activation. The involvement of Schwann cells (SCs), expressing
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Schwann cell-derived extracellular vesicles promote memory impairment associated with chronic neuropathic pain J. Neuroinflammation (IF 9.3) Pub Date : 2024-04-17 Yidan Tang, Jiahui Wu, Changliang Liu, Lu Gan, Hai Chen, Ya-Lan Sun, Jin Liu, Yuan-Xiang Tao, Tao Zhu, Chan Chen
The pathogenesis of memory impairment, a common complication of chronic neuropathic pain (CNP), has not been fully elucidated. Schwann cell (SC)-derived extracellular vesicles (EVs) contribute to remote organ injury. Here, we showed that SC-EVs may mediate pathological communication between SCs and hippocampal neurons in the context of CNP. We used an adeno-associated virus harboring the SC-specific
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Complement propagates visual system pathology following traumatic brain injury J. Neuroinflammation (IF 9.3) Pub Date : 2024-04-17 Davis M. Borucki, Baerbel Rohrer, Stephen Tomlinson
Traumatic brain injury (TBI) is associated with the development of visual system disorders. Visual deficits can present with delay and worsen over time, and may be associated with an ongoing neuroinflammatory response that is known to occur after TBI. Complement system activation is strongly associated with the neuroinflammatory response after TBI, but whether it contributes to vision loss after TBI
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LXR agonism for CNS diseases: promises and challenges J. Neuroinflammation (IF 9.3) Pub Date : 2024-04-16 Ruiyi Zhang, Emily Wuerch, V. Wee Yong, Mengzhou Xue
The unfavorable prognosis of many neurological conditions could be attributed to limited tissue regeneration in central nervous system (CNS) and overwhelming inflammation, while liver X receptor (LXR) may regulate both processes due to its pivotal role in cholesterol metabolism and inflammatory response, and thus receives increasing attentions from neuroscientists and clinicians. Here, we summarize
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GSDMD/Drp1 signaling pathway mediates hippocampal synaptic damage and neural oscillation abnormalities in a mouse model of sepsis-associated encephalopathy J. Neuroinflammation (IF 9.3) Pub Date : 2024-04-16 Qun Fu, Yi-Bao Zhang, Chang-Xi Shi, Ming Jiang, Kai Lu, Zi-Hui Fu, Jia-Ping Ruan, Jing Wu, Xiao-Ping Gu
Gasdermin D (GSDMD)-mediated pyroptotic cell death is implicated in the pathogenesis of cognitive deficits in sepsis-associated encephalopathy (SAE), yet the underlying mechanisms remain largely unclear. Dynamin-related protein 1 (Drp1) facilitates mitochondrial fission and ensures quality control to maintain cellular homeostasis during infection. This study aimed to investigate the potential role
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A P2RY12 deficiency results in sex-specific cellular perturbations and sexually dimorphic behavioral anomalies J. Neuroinflammation (IF 9.3) Pub Date : 2024-04-15 Ogochukwu J. Uweru, Akhabue K. Okojie, Aparna Trivedi, Jordan Benderoth, Lauren S. Thomas, Georgia Davidson, Kendall Cox, Ukpong B. Eyo
Microglia are sexually dimorphic, yet, this critical aspect is often overlooked in neuroscientific studies. Decades of research have revealed the dynamic nature of microglial-neuronal interactions, but seldom consider how this dynamism varies with microglial sex differences, leaving a significant gap in our knowledge. This study focuses on P2RY12, a highly expressed microglial signature gene that mediates
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Fibrin promotes oxidative stress and neuronal loss in traumatic brain injury via innate immune activation J. Neuroinflammation (IF 9.3) Pub Date : 2024-04-15 Terry Dean, Andrew S. Mendiola, Zhaoqi Yan, Rosa Meza-Acevedo, Belinda Cabriga, Katerina Akassoglou, Jae Kyu Ryu
Traumatic brain injury (TBI) causes significant blood-brain barrier (BBB) breakdown, resulting in the extravasation of blood proteins into the brain. The impact of blood proteins, especially fibrinogen, on inflammation and neurodegeneration post-TBI is not fully understood, highlighting a critical gap in our comprehension of TBI pathology and its connection to innate immune activation. We combined
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Immunotherapy with an antibody against CD1d modulates neuroinflammation in an α-synuclein transgenic model of Lewy body like disease J. Neuroinflammation (IF 9.3) Pub Date : 2024-04-15 Michiyo Iba, Somin Kwon, Changyoun Kim, Marcell Szabo, Liam Horan-Portelance, Maria Lopez-Ocasio, Pradeep Dagur, Cassia Overk, Robert A. Rissman, Eliezer Masliah
The neuroinflammatory process in synucleinopathies of the aging population such as Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) involves microglial activation as well as infiltration of the CNS by T cells and natural killer T cells (NKTs). To evaluate the potential of targeting NKT cells to modulate neuroinflammation, we treated α-syn transgenic (tg) mice (e.g.: Thy1 promoter line 61)
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Nigrostriatal degeneration determines dynamics of glial inflammatory and phagocytic activity J. Neuroinflammation (IF 9.3) Pub Date : 2024-04-12 Leyre Ayerra, Miguel Angel Abellanas, Leyre Basurco, Ibon Tamayo, Enrique Conde, Adriana Tavira, Amaya Trigo, Clara Vidaurre, Amaia Vilas, Patxi San Martin-Uriz, Esther Luquin, Pedro Clavero, Elisa Mengual, Sandra Hervás-Stubbs, Maria S. Aymerich
Glial cells are key players in the initiation of innate immunity in neurodegeneration. Upon damage, they switch their basal activation state and acquire new functions in a context and time-dependent manner. Since modulation of neuroinflammation is becoming an interesting approach for the treatment of neurodegenerative diseases, it is crucial to understand the specific contribution of these cells to
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Soluble CD27 is an intrathecal biomarker of T-cell-mediated lesion activity in multiple sclerosis J. Neuroinflammation (IF 9.3) Pub Date : 2024-04-12 Maria T. Cencioni, Roberta Magliozzi, Ilaria Palmisano, Keittisak Suwan, Antonella Mensi, Laura Fuentes-Font, Luisa M. Villar, José I. Fernández-Velasco, Noelia Villarrubia Migallón, Lucienne Costa-Frossard, Enric Monreal, Rehiana Ali, Marina Romozzi, Nicholas Mazarakis, Richard Reynolds, Richard Nicholas, Paolo A. Muraro
Soluble CD27 is a promising cerebrospinal fluid inflammatory biomarker in multiple sclerosis. In this study, we investigate relevant immune and neuro-pathological features of soluble CD27 in multiple sclerosis. Protein levels of soluble CD27 were correlated to inflammatory cell subpopulations and inflammatory cytokines and chemokines detected in cerebrospinal fluid of 137 patients with multiple sclerosis
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Correction: Advanced patient-specific microglia cell models for pre-clinical studies in Alzheimer’s disease J. Neuroinflammation (IF 9.3) Pub Date : 2024-04-10 Carla Cuní‑López, Romal Stewart, Lotta E. Oikari, Tam Hong Nguyen, Tara L. Roberts, Yifan Sun, Christine C. Guo, Michelle K. Lupton, Anthony R. White, Hazel Quek
Correction to: Journal of Neuroinflammation (2024) 21:50 https://doi.org/10.1186/s12974-024-03037-3 In this article [1], there is an error in the “Availability of data and materials” section. The SRA link in the current version of the manuscript is no longer functional and should be updated with the GEO ID provided below. All data generated and analyzed to support the findings of this study are included
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Constitutive knockout of interleukin-6 ameliorates memory deficits and entorhinal astrocytosis in the MRL/lpr mouse model of neuropsychiatric lupus J. Neuroinflammation (IF 9.3) Pub Date : 2024-04-10 Joshua Reynolds, Michelle Huang, Yaxi Li, Myriam Meineck, Tamara Moeckel, Julia Weinmann-Menke, Chandra Mohan, Andreas Schwarting, Chaim Putterman
Neuropsychiatric lupus (NPSLE) describes the cognitive, memory, and affective emotional burdens faced by many lupus patients. While NPSLE’s pathogenesis has not been fully elucidated, clinical imaging studies and cerebrospinal fluid (CSF) findings, namely elevated interleukin-6 (IL-6) levels, point to ongoing neuroinflammation in affected patients. Not only linked to systemic autoimmunity, IL-6 can
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Fascin-1 limits myosin activity in microglia to control mechanical characterization of the injured spinal cord J. Neuroinflammation (IF 9.3) Pub Date : 2024-04-10 Jinxin Huang, Xuyang Hu, Zeqiang Chen, Fangru Ouyang, Jianjian Li, Yixue Hu, Yuanzhe Zhao, Jingwen Wang, Fei Yao, Juehua Jing, Li Cheng
Mechanical softening of the glial scar region regulates axonal regeneration to impede neurological recovery in central nervous system (CNS) injury. Microglia, a crucial cellular component of the glial scar, facilitate neuronal survival and neurological recovery after spinal cord injury (SCI). However, the critical mechanical characterization of injured spinal cord that harmonizes neuroprotective function
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Impact of microglia isolation and culture methodology on transcriptional profile and function J. Neuroinflammation (IF 9.3) Pub Date : 2024-04-08 Mark Mizrachi, Betty Diamond
Microglial isolation and culturing methods continue to be explored to maximize cellular yield, purity, responsiveness to stimulation and similarity to in vivo microglia. This study aims to evaluate five different microglia isolation methods—three variants of microglia isolation from neonatal mice and two variants of microglia isolation from adult mice—on transcriptional profile and response to HMGB1
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STING inhibition suppresses microglia-mediated synapses engulfment and alleviates motor functional deficits after stroke J. Neuroinflammation (IF 9.3) Pub Date : 2024-04-08 Chaoran Wu, Shiwen Zhang, Hao Sun, Ao Li, Fengsheng Hou, Long Qi, Hong Liao
Ischemic stroke is the leading cause of adult disability. Ischemia leads to progressive neuronal death and synapse loss. The engulfment of stressed synapses by microglia further contributes to the disruption of the surviving neuronal network and related brain function. Unfortunately, there is currently no effective target for suppressing the microglia-mediated synapse engulfment. Stimulator of interferon
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Extracellular vesicle encapsulated Homer1a as novel nanotherapeutics against intracerebral hemorrhage in a mouse model J. Neuroinflammation (IF 9.3) Pub Date : 2024-04-06 Xiaowei Fei, Li Wang, Ya-nan Dou, Fei Fei, Yanyu Zhang, Weihao Lv, Xin He, Xiuquan Wu, Wangshu Chao, Hongqing Chen, Jialiang Wei, Dakuan Gao, Zhou Fei
Homer1a and A2 astrocytes are involved in the regulation of inflammation induced by intracerebral hemorrhage (ICH). However, there is no anticipated treatment strategy based on the anti-inflammatory effect of Homer1a and A2 astrocytes. Here, we successfully induced A2 astrocytes in vitro, and then we report an efficient method to prepare Homer1a+ EVs derived from A2 astrocytes which making it more
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Profiling of long non-coding RNAs in hippocampal–entorhinal system subfields: impact of RN7SL1 on neuroimmune response modulation in Alzheimer’s disease J. Neuroinflammation (IF 9.3) Pub Date : 2024-04-06 Hanyou Liu, Jingying Li, Xue Wang, Shiqi Luo, Dan Luo, Wei Ge, Chao Ma
Alzheimer’s disease (AD) is recognized as the predominant cause of dementia, and neuroimmune processes play a pivotal role in its pathological progression. The involvement of long non-coding RNAs (lncRNAs) in AD has attracted widespread attention. Herein, transcriptomic analysis of 262 unique samples extracted from five hippocampal–entorhinal system subfields of individuals with AD pathology and without
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Bi-directional neuro-immune dysfunction after chronic experimental brain injury J. Neuroinflammation (IF 9.3) Pub Date : 2024-04-05 Rodney M. Ritzel, Yun Li, Yun Jiao, Sarah J. Doran, Niaz Khan, Rebecca J. Henry, Kavitha Brunner, David J. Loane, Alan I. Faden, Gregory L. Szeto, Junfang Wu
It is well established that traumatic brain injury (TBI) causes acute and chronic alterations in systemic immune function and that systemic immune changes contribute to posttraumatic neuroinflammation and neurodegeneration. However, how TBI affects bone marrow (BM) hematopoietic stem/progenitor cells chronically and to what extent such changes may negatively impact innate immunity and neurological
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Cranial irradiation disrupts homeostatic microglial dynamic behavior J. Neuroinflammation (IF 9.3) Pub Date : 2024-04-03 Alexandra O. Strohm, Carl Johnston, Eric Hernady, Brian Marples, M. Kerry O’Banion, Ania K. Majewska
Cranial irradiation causes cognitive deficits that are in part mediated by microglia, the resident immune cells of the brain. Microglia are highly reactive, exhibiting changes in shape and morphology depending on the function they are performing. Additionally, microglia processes make dynamic, physical contacts with different components of their environment to monitor the functional state of the brain
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Metformin normalizes mitochondrial function to delay astrocyte senescence in a mouse model of Parkinson’s disease through Mfn2-cGAS signaling J. Neuroinflammation (IF 9.3) Pub Date : 2024-04-02 Min Wang, Tian Tian, Hong Zhou, Si-Yuan Jiang, Ying-Ying Jiao, Zhu Zhu, Jiang Xia, Jian-Hua Ma, Ren-Hong Du
Senescent astrocytes play crucial roles in age-associated neurodegenerative diseases, including Parkinson’s disease (PD). Metformin, a drug widely used for treating diabetes, exerts longevity effects and neuroprotective activities. However, its effect on astrocyte senescence in PD remains to be defined. Long culture-induced replicative senescence model and 1-methyl-4-phenylpyridinium/α-synuclein aggregate-induced
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Hypoxia inducible factor-1α regulates microglial innate immune memory and the pathology of Parkinson’s disease J. Neuroinflammation (IF 9.3) Pub Date : 2024-03-30 Hongtian Dong, Xiaoshuang Zhang, Yufei Duan, Yongtao He, Jiayin Zhao, Zishan Wang, Jinghui Wang, Qing Li, Guangchun Fan, Zhaolin Liu, Chenye Shen, Yunhe Zhang, Mei Yu, Jian Fei, Fang Huang
Neuroinflammation is one of the core pathological features of Parkinson’s disease (PD). Innate immune cells play a crucial role in the progression of PD. Microglia, the major innate immune cells in the brain, exhibit innate immune memory effects and are recognized as key regulators of neuroinflammatory responses. Persistent modifications of microglia provoked by the first stimuli are pivotal for innate
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The immunomodulatory effect of oral NaHCO3 is mediated by the splenic nerve: multivariate impact revealed by artificial neural networks J. Neuroinflammation (IF 9.3) Pub Date : 2024-03-28 Milena Rodriguez Alvarez, Hussam Alkaissi, Aja M. Rieger, Guillem R. Esber, Manuel E. Acosta, Stacy I. Stephenson, Allison V. Maurice, Laura Melissa Rodríguez Valencia, Christopher A. Roman, Juan Marcos Alarcon
Stimulation of the inflammatory reflex (IR) is a promising strategy for treating systemic inflammatory disorders. Recent studies suggest oral sodium bicarbonate (NaHCO3) as a potential activator of the IR, offering a safe and cost-effective treatment approach. However, the mechanisms underlying NaHCO3-induced anti-inflammatory effects remain unclear. We investigated whether oral NaHCO3’s immunomodulatory
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Changes in lipid metabolism track with the progression of neurofibrillary pathology in tauopathies J. Neuroinflammation (IF 9.3) Pub Date : 2024-03-27 Dominika Olešová, Dana Dobešová, Petra Majerová, Radana Brumarová, Aleš Kvasnička, Štěpán Kouřil, Eva Stevens, Jozef Hanes, Ľubica Fialová, Alena Michalicová, Juraj Piešťanský, Jakub Šinský, Petr Kaňovský, David Friedecký, Andrej Kováč
Accumulation of tau leads to neuroinflammation and neuronal cell death in tauopathies, including Alzheimer’s disease. As the disease progresses, there is a decline in brain energy metabolism. However, the role of tau protein in regulating lipid metabolism remains less characterized and poorly understood. We used a transgenic rat model for tauopathy to reveal metabolic alterations induced by neurofibrillary
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Liver-specific adiponectin gene therapy suppresses microglial NLRP3-inflammasome activation for treating Alzheimer’s disease J. Neuroinflammation (IF 9.3) Pub Date : 2024-03-27 Roy Chun-Laam Ng, Min Jian, Oscar Ka-Fai Ma, Ariya Weiman Xiang, Myriam Bunting, Jason Shing-Cheong Kwan, Curtis Wai-Kin Wong, Leung-Wah Yick, Sookja Kim Chung, Karen Siu-Ling Lam, Ian E. Alexander, Aimin Xu, Koon-Ho Chan
Adiponectin (APN) is an adipokine which predominantly expresses in adipocytes with neuroprotective and anti-inflammatory effects. We have recently indicated that circulatory trimeric APN can enter the brain by crossing the blood–brain barrier (BBB) and modulate microglia-mediated neuroinflammation. Here, we found that the microglial NLR family pyrin domain containing 3 (NLRP3)-inflammasome activation
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Single-cell RNA sequencing reveals the immune features and viral tropism in the central nervous system of mice infected with Japanese encephalitis virus J. Neuroinflammation (IF 9.3) Pub Date : 2024-03-26 Ling’en Yang, Junyao Xiong, Yixin Liu, Yinguang Liu, Xugang Wang, Youhui Si, Bibo Zhu, Huanchun Chen, Shengbo Cao, Jing Ye
Japanese encephalitis virus (JEV) is a neurotropic pathogen that causes lethal encephalitis. The high susceptibility and massive proliferation of JEV in neurons lead to extensive neuronal damage and inflammation within the central nervous system. Despite extensive research on JEV pathogenesis, the effect of JEV on the cellular composition and viral tropism towards distinct neuronal subtypes in the
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Wnt5a/β-catenin-mediated epithelial-mesenchymal transition: a key driver of subretinal fibrosis in neovascular age-related macular degeneration J. Neuroinflammation (IF 9.3) Pub Date : 2024-03-26 Dandan Liu, Jingxiao Du, Hai Xie, Haibin Tian, Lixia Lu, Chaoyang Zhang, Guo-Tong Xu, Jingfa Zhang
Neovascular age-related macular degeneration (nAMD), accounts for up to 90% of AMD-associated vision loss, ultimately resulting in the formation of fibrotic scar in the macular region. The pathogenesis of subretinal fibrosis in nAMD involves the process of epithelial–mesenchymal transition (EMT) occurring in retinal pigment epithelium (RPE). Here, we aim to investigate the underlying mechanisms involved
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The mouse retinal pigment epithelium mounts an innate immune defense response following retinal detachment J. Neuroinflammation (IF 9.3) Pub Date : 2024-03-25 Steven F. Abcouwer, Bruna Miglioranza Scavuzzi, Phillip E. Kish, Dejuan Kong, Sumathi Shanmugam, Xuan An Le, Jingyu Yao, Heather Hager, David N Zacks
The retinal pigment epithelium (RPE) maintains photoreceptor viability and function, completes the visual cycle, and forms the outer blood-retinal barrier (oBRB). Loss of RPE function gives rise to several monogenic retinal dystrophies and contributes to age-related macular degeneration. Retinal detachment (RD) causes separation of the neurosensory retina from the underlying RPE, disrupting the functional
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P2X7 receptor antagonists modulate experimental autoimmune neuritis via regulation of NLRP3 inflammasome activation and Th17 and Th1 cell differentiation J. Neuroinflammation (IF 9.3) Pub Date : 2024-03-25 Yuhan Xie, Ranran Han, Yulin Li, Weiya Li, Shichao Zhang, Yu Wu, Yuexin Zhao, Rongrong Liu, Jie Wu, Wei Jiang, Xiuju Chen
Guillain–Barré syndrome (GBS), a post-infectious, immune-mediated, acute demyelinating disease of the peripheral nerves and nerve roots, represents the most prevalent and severe acute paralyzing neuropathy. Purinergic P2X7 receptors (P2X7R) play a crucial role in central nervous system inflammation. However, little is known about their role in the immune-inflammatory response within the peripheral
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Inflammation-induced TRPV4 channels exacerbate blood–brain barrier dysfunction in multiple sclerosis J. Neuroinflammation (IF 9.3) Pub Date : 2024-03-23 Cathrin E. Hansen, Alwin Kamermans, Kevin Mol, Kristina Berve, Carla Rodriguez-Mogeda, Wing Ka Fung, Bert van het Hof, Ruud D. Fontijn, Susanne M. A. van der Pol, Laura Michalick, Wolfgang M. Kuebler, Boyd Kenkhuis, Willeke van Roon-Mom, Wolfgang Liedtke, Britta Engelhardt, Gijs Kooij, Maarten E. Witte, Helga E. de Vries
Blood–brain barrier (BBB) dysfunction and immune cell migration into the central nervous system (CNS) are pathogenic drivers of multiple sclerosis (MS). Ways to reinstate BBB function and subsequently limit neuroinflammation present promising strategies to restrict disease progression. However, to date, the molecular players directing BBB impairment in MS remain poorly understood. One suggested candidate
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Cryopreservation of cerebrospinal fluid cells preserves the transcriptional landscape for single-cell analysis J. Neuroinflammation (IF 9.3) Pub Date : 2024-03-23 Mahesh Chandra Kodali, Jerry Antone, Eric Alsop, Rojashree Jayakumar, Khushi Parikh, Aude Chiot, Paula Sanchez-Molina, Bahareh Ajami, Steven E. Arnold, Kendall Jensen, Sudeshna Das, Marc S. Weinberg
Cerebrospinal fluid (CSF) matrix biomarkers have become increasingly valuable surrogate markers of neuropsychiatric diseases in research and clinical practice. In contrast, CSF cells have been rarely investigated due to their relative scarcity and fragility, and lack of common collection and cryopreservation protocols, with limited exceptions for neurooncology and primary immune-based diseases like
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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 J. Neuroinflammation (IF 9.3) Pub Date : 2024-03-21 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
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Deletion of Slc9a1 in Cx3cr1+ cells stimulated microglial subcluster CREB1 signaling and microglia-oligodendrocyte crosstalk J. Neuroinflammation (IF 9.3) Pub Date : 2024-03-20 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
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Macrophages coordinate immune response to laser-induced injury via extracellular traps J. Neuroinflammation (IF 9.3) Pub Date : 2024-03-18 Federica M. Conedera, Despina Kokona, Martin S. Zinkernagel, Jens V. Stein, Charles P. Lin, Clemens Alt, Volker Enzmann
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
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Border-associated macrophages in the central nervous system J. Neuroinflammation (IF 9.3) Pub Date : 2024-03-13 Rui Sun, Haowu Jiang
Tissue-resident macrophages play an important role in the local maintenance of homeostasis and immune surveillance. In the central nervous system (CNS), brain macrophages are anatomically divided into parenchymal microglia and non-parenchymal border-associated macrophages (BAMs). Among these immune cell populations, microglia have been well-studied for their roles during development as well as in health
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TYROBP/DAP12 knockout in Huntington’s disease Q175 mice cell-autonomously decreases microglial expression of disease-associated genes and non-cell-autonomously mitigates astrogliosis and motor deterioration J. Neuroinflammation (IF 9.3) Pub Date : 2024-03-08 Jordi Creus-Muncunill, Jean Vianney Haure-Mirande, Daniele Mattei, Joanna Bons, Angie V. Ramirez, B. Wade Hamilton, Chuhyon Corwin, Sarah Chowdhury, Birgit Schilling, Lisa M. Ellerby, Michelle E. Ehrlich
Huntington’s disease (HD) is a fatal neurodegenerative disorder caused by an expansion of the CAG trinucleotide repeat in the Huntingtin gene (HTT). Immune activation is abundant in the striatum of HD patients. Detection of active microglia at presymptomatic stages suggests that microgliosis is a key early driver of neuronal dysfunction and degeneration. Recent studies showed that deletion of Tyrobp
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Role of myeloid cells in ischemic retinopathies: recent advances and unanswered questions J. Neuroinflammation (IF 9.3) Pub Date : 2024-03-07 Rami A. Shahror, Carol A. Morris, Aya A. Mohammed, Melissa Wild, Bushra Zaman, Christian D. Mitchell, Paul H. Phillips, Nancy J. Rusch, Esraa Shosha, Abdelrahman Y. Fouda
Myeloid cells including microglia and macrophages play crucial roles in retinal homeostasis by clearing cellular debris and regulating inflammation. These cells are activated in several blinding ischemic retinal diseases including diabetic retinopathy, where they may exert both beneficial and detrimental effects on neurovascular function and angiogenesis. Myeloid cells impact the progression of retinal
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The contribution of pattern recognition receptor signalling in the development of age related macular degeneration: the role of toll-like-receptors and the NLRP3-inflammasome J. Neuroinflammation (IF 9.3) Pub Date : 2024-03-05 Alice Brandli, Kirstan A. Vessey, Erica L. Fletcher
Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss, characterised by the dysfunction and death of the photoreceptors and retinal pigment epithelium (RPE). Innate immune cell activation and accompanying para-inflammation have been suggested to contribute to the pathogenesis of AMD, although the exact mechanism(s) and signalling pathways remain elusive. Pattern recognition
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Single-cell RNA sequencing reveals peripheral blood leukocyte responses to spinal cord injury in mice with humanised immune systems J. Neuroinflammation (IF 9.3) Pub Date : 2024-03-01 Ellen R. Gillespie, Laura F. Grice, Isabel G. Courtney, Hong Wa Lao, Woncheol Jung, Sonny Ramkomuth, Jacky Xie, David A. Brown, James Walsham, Kristen J. Radford, Quan H. Nguyen, Marc J. Ruitenberg
Next-generation humanised mouse models and single-cell RNA sequencing (scRNAseq) approaches enable in-depth studies into human immune cell biology. Here we used NSG-SGM3 mice engrafted with human umbilical cord haematopoietic stem cells to investigate how human immune cells respond to and/or are changed by traumatic spinal cord injury (SCI). We hypothesised that the use of such mice could help advance
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Human serum-derived α-synuclein auto-antibodies mediate NMDA receptor-dependent degeneration of CNS neurons J. Neuroinflammation (IF 9.3) Pub Date : 2024-02-28 Pretty Garg, Franziska Würtz, Fabian Hobbie, Klemens Buttgereit, Abhishek Aich, Kristian Leite, Peter Rehling, Sebastian Kügler, Mathias Bähr
Presence of autoantibodies against α-synuclein (α-syn AAb) in serum of the general population has been widely reported. That such peripheral factors may be involved in central nervous system pathophysiology was demonstrated by detection of immunoglobulins (IgGs) in cerebrospinal fluid and brain of Parkinson’s disease (PD) patients. Thus, blood-borne IgGs may reach the brain parenchyma through an impaired
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Inhibition of MMP8 effectively alleviates manic-like behavior and reduces neuroinflammation by modulating astrocytic CEBPD J. Neuroinflammation (IF 9.3) Pub Date : 2024-02-28 Tzu-Yun Wang, Eddie Feng-Ju Weng, Yun-Chen Hsu, Lu-Ping Shiu, Teng-Wei Huang, Hsuan-Cheng Wu, Jau-Shyong Hong, Shao-Ming Wang
There is an intrinsic relationship between psychiatric disorders and neuroinflammation, including bipolar disorder. Ouabain, an inhibitor of Na+/K+-ATPase, has been implicated in the mouse model with manic-like behavior. However, the molecular mechanisms linking neuroinflammation and manic-like behavior require further investigation. CCAAT/Enhancer-Binding Protein Delta (CEBPD) is an inflammatory transcription
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IL-6 from cerebrospinal fluid causes widespread pain via STAT3-mediated astrocytosis in chronic constriction injury of the infraorbital nerve J. Neuroinflammation (IF 9.3) Pub Date : 2024-02-28 Ning Yu, Huan Cui, Sixuan Jin, Penghao Liu, Yehong Fang, Fengrun Sun, Yan Cao, Bo Yuan, Yikuan Xie, Wanru Duan, Chao Ma
The spinal inflammatory signal often spreads to distant segments, accompanied by widespread pain symptom under neuropathological conditions. Multiple cytokines are released into the cerebrospinal fluid (CSF), potentially inducing the activation of an inflammatory cascade at remote segments through CSF flow. However, the detailed alteration of CSF in neuropathic pain and its specific role in widespread
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Elevated SLC7A2 expression is associated with an abnormal neuroinflammatory response and nitrosative stress in Huntington’s disease J. Neuroinflammation (IF 9.3) Pub Date : 2024-02-28 Ian D. Gaudet, Hongyuan Xu, Emily Gordon, Gianna A. Cannestro, Michael L. Lu, Jianning Wei
We previously identified solute carrier family 7 member 2 (SLC7A2) as one of the top upregulated genes when normal Huntingtin was deleted. SLC7A2 has a high affinity for l-arginine. Arginine is implicated in inflammatory responses, and SLC7A2 is an important regulator of innate and adaptive immunity in macrophages. Although neuroinflammation is clearly demonstrated in animal models and patients with
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Differential contribution of THIK-1 K+ channels and P2X7 receptors to ATP-mediated neuroinflammation by human microglia J. Neuroinflammation (IF 9.3) Pub Date : 2024-02-26 Ali Rifat, Bernardino Ossola, Roland W. Bürli, Lee A. Dawson, Nicola L. Brice, Anna Rowland, Marina Lizio, Xiao Xu, Keith Page, Pawel Fidzinski, Julia Onken, Martin Holtkamp, Frank L. Heppner, Jörg R. P. Geiger, Christian Madry
Neuroinflammation is highly influenced by microglia, particularly through activation of the NLRP3 inflammasome and subsequent release of IL-1β. Extracellular ATP is a strong activator of NLRP3 by inducing K+ efflux as a key signaling event, suggesting that K+-permeable ion channels could have high therapeutic potential. In microglia, these include ATP-gated THIK-1 K+ channels and P2X7 receptors, but
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SPOCK2 modulates neuropathic pain by interacting with MT1-MMP to regulate astrocytic MMP-2 activation in rats with chronic constriction injury J. Neuroinflammation (IF 9.3) Pub Date : 2024-02-22 Chenglong Wang, Yitong Xu, Miao Xu, Cong Sun, Xiaojiao Zhang, Xueshu Tao, Tao Song
Neuropathic pain (NP) is a kind of intractable pain. The pathogenesis of NP remains a complicated issue for pain management practitioners. SPARC/osteonectin, CWCV, and Kazal-like domains proteoglycan 2 (SPOCK2) are members of the SPOCK family that play a significant role in the development of the central nervous system. In this study, we investigated the role of SPOCK2 in the development of NP in a
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Gliosis-dependent expression of complement factor H truncated variants attenuates retinal neurodegeneration following ischemic injury J. Neuroinflammation (IF 9.3) Pub Date : 2024-02-22 Josef Biber, Yassin Jabri, Sarah Glänzer, Aaron Dort, Patricia Hoffelner, Christoph Q. Schmidt, Oliver Bludau, Diana Pauly, Antje Grosche
Inherited, age-related, and acute retinal diseases are often exacerbated by an aberrant or excessive activity of the complement system. Consequently, cells not directly affected by an acute event or genetic variants may degenerate, resulting in enhanced visual impairment. The therapeutic potential of supplementation of complement factor H (FH), a key regulator of the complement cascade, is therefore
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Dimethyl fumarate improves cognitive impairment and neuroinflammation in mice with Alzheimer’s disease J. Neuroinflammation (IF 9.3) Pub Date : 2024-02-21 Ting Wang, Akira Sobue, Seiji Watanabe, Okiru Komine, Takaomi C. Saido, Takashi Saito, Koji Yamanaka
Neuroinflammation substantially contributes to the pathology of Alzheimer’s disease (AD), the most common form of dementia. Studies have reported that nuclear factor erythroid 2-related factor 2 (Nrf2) attenuates neuroinflammation in the mouse models of neurodegenerative diseases, however, the detailed mechanism remains unclear. The effects of dimethyl fumarate (DMF), a clinically used drug to activate
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Parkinson’s disease-derived α-synuclein assemblies combined with chronic-type inflammatory cues promote a neurotoxic microglial phenotype J. Neuroinflammation (IF 9.3) Pub Date : 2024-02-21 Cansu Yildirim-Balatan, Alexis Fenyi, Pierre Besnault, Lina Gomez, Julia E. Sepulveda-Diaz, Patrick P. Michel, Ronald Melki, Stéphane Hunot
Parkinson’s disease (PD) is a common age-related neurodegenerative disorder characterized by the aggregation of α-Synuclein (αSYN) building up intraneuronal inclusions termed Lewy pathology. Mounting evidence suggests that neuron-released αSYN aggregates could be central to microglial activation, which in turn mounts and orchestrates neuroinflammatory processes potentially harmful to neurons. Therefore
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Integration of National Health Insurance claims data and animal models reveals fexofenadine as a promising repurposed drug for Parkinson’s disease J. Neuroinflammation (IF 9.3) Pub Date : 2024-02-21 Jae-Bong Kim, Yujeong Kim, Soo-Jeong Kim, Tae‑Young Ha, Dong-Kyu Kim, Dong Won Kim, Minyoung So, Seung Ho Kim, Hyun Goo Woo, Dukyong Yoon, Sang Myun Park
Parkinson’s disease (PD) is a common and costly progressive neurodegenerative disease of unclear etiology. A disease-modifying approach that can directly stop or slow its progression remains a major unmet need in the treatment of PD. A clinical pharmacology-based drug repositioning strategy is a useful approach for identifying new drugs for PD. We analyzed claims data obtained from the National Health
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Combination protein biomarkers predict multiple sclerosis diagnosis and outcomes J. Neuroinflammation (IF 9.3) Pub Date : 2024-02-17 Eleftheria Kodosaki, W. John Watkins, Sam Loveless, Karim L. Kreft, Aidan Richards, Valerie Anderson, Lisa Hurler, Neil P. Robertson, Wioleta M. Zelek, Emma C. Tallantyre
Establishing biomarkers to predict multiple sclerosis diagnosis and prognosis has been challenging using a single biomarker approach. We hypothesised that a combination of biomarkers would increase the accuracy of prediction models to differentiate multiple sclerosis from other neurological disorders and enhance prognostication for people with multiple sclerosis. We measured 24 fluid biomarkers in
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The insular cortex is not insular in thyroid eye disease: neuroimaging revelations of central–peripheral system interaction J. Neuroinflammation (IF 9.3) Pub Date : 2024-02-17 Haiyang Zhang, Yuting Liu, Duojin Xia, Mengda Jiang, Yinwei Li, Jing Sun, Haixia Guan, Ling Zhu, Xuefei Song, Jue Wang, Xianqun Fan, Huifang Zhou
Thyroid eye disease (TED) is highly correlated with dysregulated immunoendocrine status. The insular cortex was found to regulate peripheral inflammation and immunomodulation in mice. This study aimed to explore whether the insular cortex in patients with TED played a modulatory role including the aberrant brain functional alteration and its association with immunoendocrine status. This study included
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Advanced patient-specific microglia cell models for pre-clinical studies in Alzheimer’s disease J. Neuroinflammation (IF 9.3) Pub Date : 2024-02-15 Carla Cuní-López, Romal Stewart, Lotta E. Oikari, Tam Hong Nguyen, Tara L. Roberts, Yifan Sun, Christine C. Guo, Michelle K. Lupton, Anthony R. White, Hazel Quek
Alzheimer’s disease (AD) is an incurable neurodegenerative disorder with a rapidly increasing prevalence worldwide. Current approaches targeting hallmark pathological features of AD have had no consistent clinical benefit. Neuroinflammation is a major contributor to neurodegeneration and hence, microglia, the brain’s resident immune cells, are an attractive target for potentially more effective therapeutic
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Intracerebellar injection of monocytic immature myeloid cells prevents the adverse effects caused by stereotactic surgery in a model of cerebellar neurodegeneration J. Neuroinflammation (IF 9.3) Pub Date : 2024-02-14 Carlos del Pilar, Lucía Garrido-Matilla, Lucía del Pozo-Filíu, Rafael Lebrón-Galán, Raúl F. Arias, Diego Clemente, José Ramón Alonso, Eduardo Weruaga, David Díaz
Myeloid-derived suppressor cells (MDSCs) constitute a recently discovered bone-marrow-derived cell type useful for dealing with neuroinflammatory disorders. However, these cells are only formed during inflammatory conditions from immature myeloid cells (IMCs) that acquire immunosuppressive activity, thus being commonly gathered from diseased animals. Then, to obtain a more clinically feasible source
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The role of CD56bright NK cells in neurodegenerative disorders J. Neuroinflammation (IF 9.3) Pub Date : 2024-02-13 Carla Rodriguez-Mogeda, Chaja M. J. van Ansenwoude, Lennart van der Molen, Eva M. M. Strijbis, Reina E. Mebius, Helga E. de Vries
Emerging evidence suggests a potential role for natural killer (NK) cells in neurodegenerative diseases, such as multiple sclerosis, Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis. However, the precise function of NK cells in these diseases remains ambiguous. The existence of two NK cell subsets, CD56bright and CD56dim NK cells, complicates the understanding of the contribution
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Progranulin haploinsufficiency mediates cytoplasmic TDP-43 aggregation with lysosomal abnormalities in human microglia J. Neuroinflammation (IF 9.3) Pub Date : 2024-02-13 Wonjae Sung, Min-Young Noh, Minyeop Nahm, Yong Sung Kim, Chang-Seok Ki, Young-Eun Kim, Hee-Jin Kim, Seung Hyun Kim
Progranulin (PGRN) haploinsufficiency due to progranulin gene (GRN) variants can cause frontotemporal dementia (FTD) with aberrant TAR DNA-binding protein 43 (TDP-43) accumulation. Despite microglial burden with TDP-43-related pathophysiology, direct microglial TDP-43 pathology has not been clarified yet, only emphasized in neuronal pathology. Thus, the objective of this study was to investigate TDP-43