Article
Multidisciplinary Sciences
Narayana Yadavalli, Shawn M. Ferguson
Summary: This study reveals that LRRK2 negatively regulates lysosome degradative activity in macrophages and microglia through transcriptional mechanisms. Depletion or inhibition of LRRK2 enhances lysosomal proteolytic activity and expression of lysosomal hydrolases, while the Parkinson's disease mutant LRRK2 G2019S suppresses lysosomal degradative activity and gene expression. MiT-TFE transcription factors are identified as mediators of LRRK2-dependent control of lysosomal gene expression.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Review
Geriatrics & Gerontology
Yun Wei, Xianxiao Li
Summary: Microglia, immune-competent cells, play a critical role in maintaining normal brain function. In Alzheimer's disease, microglial proliferation and activation occur around amyloid plaques. Recent research has discovered various microglial phenotypes related to aging and Alzheimer's disease, beyond the traditional M1 and M2 types. Redox signaling regulates the acquisition of different microglial activation phenotypes, which are associated with distinct molecular signatures.
Article
Neurosciences
Yunting Zhu, Maree J. Webster, Caitlin E. Murphy, Frank A. Middleton, Paul T. Massa, Chunyu Liu, Rujia Dai, Cyndi Shannon Weickert
Summary: Quiescent microglia and increased pro-inflammatory macrophages co-exist in the cortex of people with schizophrenia.
FRONTIERS IN NEUROSCIENCE
(2022)
Review
Immunology
Wissam Beaino, Bieneke Janssen, Danielle J. Vugts, Helga E. de Vries, Albert D. Windhorst
Summary: There is increasing evidence showing the heterogeneity of microglia activation in neuroinflammatory and neurodegenerative diseases. Pro-inflammatory microglia are believed to be detrimental while anti-inflammatory microglia may aid in damage repair. PET imaging shows potential for non-invasive quantification of neuroinflammation and discrimination between microglia phenotypes, but obstacles remain in targeting specific markers for selective imaging.
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
(2021)
Review
Cell Biology
Menbere Y. Wendimu, Shelley B. Hooks
Summary: Neuroinflammation plays a fundamental role in neurodegenerative diseases, and microglia, as the immune guardians of the central nervous system, are central drivers of this inflammation. Microglia exhibit complex and often contradictory activation patterns in different pathological states, playing both detrimental and protective roles.
Article
Engineering, Biomedical
Yilun Luo, Xiaowen Zheng, Peiqi Yuan, Xingyao Ye, Lie Ma
Summary: This study introduces a novel strategy for spatiotemporal manipulation of macrophage phenotypes using a UV-induced dynamic Arg-Gly-Asp (RGD) pattern, which sequentially modulates macrophage morphology and phenotype transitions, leading to enhanced anti-inflammatory processes.
BIOACTIVE MATERIALS
(2021)
Article
Neurosciences
Hui Li, Feng Wang, Xuqi Guo, Yugang Jiang
Summary: Our study identified that autophagy-related genes in Alzheimer's disease are regulated by MEF2A and correlated with pathological progression. Increased methylation level of MEF2A enhancer is associated with reduced expression of MEF2A and downregulation of autophagy-related genes in AD.
FRONTIERS IN NEUROSCIENCE
(2021)
Review
Clinical Neurology
Michael Candlish, Jasmin K. Hefendehl
Summary: Microglia, the primary immune cells of the central nervous system, undergo an aging process that impairs their ability to perform vital functions. They transition from a homeostatic state to an activated state in response to insults and aging, showing diverse responses to stimuli such as acute injury or chronic disease. This complexity is further influenced by the distinct alterations that occur in the aging process.
FRONTIERS IN NEUROLOGY
(2021)
Article
Pharmacology & Pharmacy
Jiping Li, Xinping Dai, Liuyi Zhou, Xinxiu Li, Dongxiao Pan
Summary: This study demonstrates that Edaravone (EDA) can improve neurobehavioral functions and alleviate neuroinflammation in a rat model of Parkinson's disease by inhibiting NLRP3 inflammasome activation and regulating microglia M1/M2 polarization.
FRONTIERS IN PHARMACOLOGY
(2021)
Editorial Material
Biochemistry & Molecular Biology
Edward S. Wickstead, Murray A. Irving, Stephen J. Getting, Simon McArthur
Summary: Alzheimer's disease and dementia pose significant healthcare challenges, with neuroinflammation playing a key role in disease development. Regulating microglial activity may be a promising therapeutic strategy, with the receptor FPR2 identified as a valuable target for investigation in Alzheimer's disease.
Article
Geriatrics & Gerontology
Zejie Zuo, Fangfang Qi, Zhiwei Xing, Lifang Yuan, Yunjie Yang, Zitian He, Lihua Zhou, Zhibin Yao
Summary: The study suggests that A beta immunotherapy may exacerbate vascular A beta-associated pathology in Alzheimer's disease, whereas BCG treatment can improve this condition and enhance the efficacy of A beta vaccine. BCG treatment not only enhances the phagocytosis of A beta but also alleviates pathological changes by recruiting protective monocytes.
NEUROBIOLOGY OF AGING
(2021)
Review
Immunology
Quxing Wei, Yanyue Deng, Qianqian Yang, Angyu Zhan, Lexun Wang
Summary: Macrophages play diverse roles in physiological and pathological conditions, particularly in metabolic disorders, and have become promising targets for diagnosis and therapy. Due to their heterogeneity and polarization, the phenotypes and functions of macrophages in metabolic disorders are complex. The development of specific molecular markers in macrophage research has greatly contributed to understanding their role in metabolic disorders. This review analyzes commonly used and novel macrophage markers related to metabolic disorders, aiming to improve their utilization in research.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Shogo Moriya, Michiko Hanazono, Takeshi Fukuhara, Katsuro Iwase, Nobutaka Hattori, Masaki Takiguchi
Summary: This study investigated the involvement of macrophages/microglia in the formation and spread of alpha-synuclein (αS) fibrils. Transgenic zebrafish expressing αS in macrophages/microglia showed accumulation of αS in neurons. Transcriptome analysis revealed changes in gene expression related to kinases, ubiquitin protein ligases, neuronal activity, and transport. Furthermore, αS fibrils formed from monomers in macrophages and were spread to neurons. The ubiquitin-proteasome system modulated αS fibrils. These findings suggest that macrophages play an essential role in the formation of αS aggregates and the pathogenesis of Parkinson's disease.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Zhiwei Xue, Lei Ye, Jianwei Ge, Zhen Lan, Xinxin Zou, Chenglu Mao, Xinyu Bao, Linjie Yu, Yun Xu, Xiaolei Zhu
Summary: In this study, the researchers found that the inhibition of ABHD6 could improve synaptic function and memory impairment in APP/PS1 mice with Alzheimer's disease, without affecting the levels of amyloid-beta and neuroinflammation in the brain. Injection of the ABHD6-specific inhibitor wwl70 enhanced synaptic plasticity and memory function, lowered amyloid-beta levels and neuroinflammation, and promoted the phagocytosis of amyloid-beta by microglia.
PHARMACOLOGICAL RESEARCH
(2023)
Article
Cell Biology
Barbara M. Fenner, Mark E. Fenner, Natalie Prowse, Shawn P. Hayley
Summary: A novel in vitro classification system was developed to track microglial activation state and neurotoxicity, revealing the importance of LRRK2 and WAVE2 as mediators of microglial-induced neurotoxicity.
JOURNAL OF CELLULAR PHYSIOLOGY
(2022)
Article
Multidisciplinary Sciences
Martin W. Breuss, Xiaoxu Yang, Johannes C. M. Schlachetzki, Danny Antaki, Addison J. Lana, Xin Xu, Changuk Chung, Guoliang Chai, Valentina Stanley, Qiong Song, Traci F. Newmeyer, An Nguyen, Sydney O'Brien, Marten A. Hoeksema, Beibei Cao, Alexi Nott, Jennifer McEvoy-Venneri, Martina P. Pasillas, Scott T. Barton, Brett R. Copeland, Shareef Nahas, Lucitia Van der Kraan, Yan Ding, Christopher K. Glass, Joseph G. Gleeson
Summary: The structure of the human neocortex and its developmental processes were investigated through the assessment of brain somatic mosaicism. Samples from adult human tissues were analyzed, revealing distinct geographical, cell-type, and Glade organizations in the brain and other organs. The findings suggest that the clones in the cerebral cortex respect the midline axis and have dual origins from both dorsal and ventral cellular populations.
Correction
Biochemistry & Molecular Biology
Ryan J. Weiss, Philipp N. Spahn, Austin W. T. Chiang, Qing Liu, Jing Li, Kristina M. Hamill, Sandra Rother, Thomas M. Clausen, Marten A. Hoeksema, Bryce M. Timm, Kamil Godula, Christopher K. Glass, Yitzhak Tor, Philip L. S. M. Gordts, Nathan E. Lewis, Jeffrey D. Esko
NATURE CHEMICAL BIOLOGY
(2022)
Article
Cell Biology
Isidoro Cobo, Anyan Cheng, Jessica Murillo-Saich, Roxana Coras, Alyssa Torres, Yohei Abe, Addison J. Lana, Johannes Schlachetzki, Ru Liu-Bryan, Robert Terkeltaub, Elsa Sanchez-Lopez, Christopher K. Glass, Monica Guma
Summary: MSUc induces a metabolic-inflammatory response in non-primed macrophages, leading to metabolic rewiring in gouty arthritis patients and mice. This response is regulated by JUN and JNK signaling and is independent of LPS stimulation and inflammasome activation.
Article
Immunology
Isidoro Cobo, Tiffany N. Tanaka, Kailash Chandra Mangalhara, Addison Lana, Calvin Yeang, Claudia Han, Johannes Schlachetzki, Jean Challcombe, Bethany R. Fixsen, Mashito Sakai, Rick Z. Li, Hannah Fields, Michal Mokry, Randy G. Tsai, Rafael Bejar, Koen Prange, Menno de Winther, Gerald S. Shadel, Christopher K. Glass
Summary: Loss of function mutations in DNMT3A and TET2 result in a type I interferon response, leading to increased risk of cardiovascular disease. These mutations impair mitochondrial DNA integrity and activate the cGAS signaling pathway. DNMT3A and TET2 regulate the expression of transcription factor A mitochondria by interacting with RBPJ and ZNF143, thereby maintaining mitochondrial DNA integrity.
Article
Medicine, Research & Experimental
Peng Zhao, Xiaoli Sun, Zhongji Liao, Hong Yu, Dan Li, Zeyang Shen, Christopher K. Glass, Joseph L. Witztum, Alan R. Saltiel
Summary: Amlexanox has the potential to improve diet-induced hypertriglyceridemia atherogenesis through synergistic actions involving upregulation of bile acid synthesis, reduction of inflammation, and improvement of vascular dysfunction.
Article
Cell Biology
Larissa Traxler, Joseph R. Herdy, Davide Stefanoni, Sophie Eichhorner, Silvia Pelucchi, Attila Szucs, Alice Santagostino, Yongsung Kim, Ravi K. Agarwal, Johannes C. M. Schlachetzki, Christopher K. Glass, Jessica Lagerwall, Douglas Galasko, Fred H. Gage, Angelo D'Alessandro, Jerome Mertens
Summary: This study investigated the metabolic changes and transcriptional alterations in sporadic Alzheimer's disease (AD) utilizing induced neurons (iNs) from AD patients. The pathological isoform switching of PKM2 was found to contribute to neuronal vulnerability and loss in AD. Chemical modulation of PKM2 could reverse these changes and enhance neuronal resilience against cell death.
Article
Immunology
Zsolt Czimmerer, Laszlo Halasz, Bence Daniel, Zsofia Varga, Krisztian Bene, Apolka Domokos, Marten Hoeksema, Zeyang Shen, Wilhelm K. Berger, Timea Cseh, Karoly Jambrovics, Zsuzsanna Kolostyak, Ferenc Fenyvesi, Judit Varadi, Szilard Poliska, Gyorgy Hajas, Istvan Szatmari, Christopher K. Glass, Attila Bacsi, Laszlo Nagy
Summary: Prior exposure to microenvironmental signals can alter the response of macrophages. IL-4-polarized macrophages were found to exhibit hyperinflammatory gene expression upon LPS exposure, contrary to previous beliefs. This extended synergy was supported by epigenomic remodeling, NF-kappa B-p65 cistrome expansion, and increased enhancer activity.
Article
Neurosciences
Kristina Battis, Jazmin B. Florio, Michael Mante, Addison Lana, Isabel Naumann, Carina Gauer, Vera Lambrecht, Simon Julian Mueller, Isidoro Cobo, Bethany Fixsen, Ha Yeon Kim, Eliezer Masliah, Christopher K. Glass, Johannes C. M. Schlachetzki, Robert A. Rissman, Juergen Winkler, Alana Hoffmann
Summary: This study reveals the complex role of myeloid cells in multiple system atrophy and emphasizes the importance of balancing their beneficial and adverse effects before clinical translation.
JOURNAL OF NEUROSCIENCE
(2022)
Review
Gastroenterology & Hepatology
Daniel Q. Huang, Michael Downes, Ronald M. Evans, Joseph L. Witztum, Christopher K. Glass, Rohit Loomba
Summary: The global burden of nonalcoholic fatty liver disease (NAFLD) is increasing, with individuals with NAFLD at higher risk for cardiovascular disease, sharing multiple disease mechanisms.
SEMINARS IN LIVER DISEASE
(2022)
Article
Cell & Tissue Engineering
Joseph R. Herdy, Larissa Traxler, Ravi K. Agarwal, Lukas Karbacher, Johannes C. M. Schlachetzki, Lena Boehnke, Dina Zangwill, Doug Galasko, Christopher K. Glass, Jerome Mertens, Fred H. Gage
Summary: The concept of senescence extends beyond proliferating cells, as senescence-like features have been observed in neurons, including those affected by Alzheimer's disease. Targeting senescent neurons could be a strategy for preventing or treating AD.
Article
Neurosciences
Johannes C. M. Schlachetzki, Yi Zhou, Christopher K. Glass
Summary: Cognitive impairment is prevalent in individuals with HIV despite antiretroviral therapy, with evidence suggesting that the brain may serve as a sanctuary for HIV persistence. Recent advances in understanding the diversity of microglia in HIV, including their epigenome, transcriptome, and function, highlight their potential role in driving HIV-associated neurocognitive disorders.
CURRENT OPINION IN NEUROBIOLOGY
(2022)
Article
Multidisciplinary Sciences
Kei-ichiro Arimoto, Sayuri Miyauchi, Ty D. Troutman, Yue Zhang, Mengdan Liu, Samuel A. Stoner, Amanda G. Davis, Jun-Bao Fan, Yi-Jou Huang, Ming Yan, Christopher K. Glass, Dong-Er Zhang
Summary: Immunotherapy is an effective cancer treatment, but not for all patients, prompting the need for alternative strategies. Inducing cancer immunogenic cell death (ICD) shows promise in promoting robust immune responses against tumor-associated antigens. Depletion of USP18, a negative regulator of interferon signaling, selectively induces ICD in cancer cells, suggesting targeting USP18 as a potential cancer immunotherapy.
NATURE COMMUNICATIONS
(2023)
Article
Immunology
Hunter Bennett, Ty D. Troutman, Enchen Zhou, Nathanael J. Spann, Verena M. Link, Jason S. Seidman, Christian K. Nickl, Yohei Abe, Mashito Sakai, Martina P. Pasillas, Justin M. Marlman, Carlos Guzman, Mojgan Hosseini, Bernd Schnabl, Christopher K. Glass
Summary: This study reveals the impact of noncoding genetic variation on Kupffer cell phenotypes and identifies environmental factors that contribute to this variation. The study also differentiates between cell-autonomous and non-cell-autonomous effects of genetic variation. Additionally, the study demonstrates that epigenetic landscapes can provide insight into the trans effects of genetic variation and serve as a resource for further understanding genetic control of transcription in Kupffer cells and macrophages in vitro.
Review
Neurosciences
Rosa C. Paolicelli, Amanda Sierra, Beth Stevens, Marie-Eve Tremblay, Adriano Aguzzi, Bahareh Ajami, Ido Amit, Etienne Audinat, Ingo Bechmann, Mariko Bennett, Frederick Bennett, Alain Bessis, Knut Biber, Staci Bilbo, Mathew Blurton-Jones, Erik Boddeke, Dora Brites, Bert Brone, Guy C. Brown, Oleg Butovsky, Monica J. Carson, Bernardo Castellano, Marco Colonna, Sally A. Cowley, Colm Cunningham, Dimitrios Davalos, Philip L. De Jager, Bart de Strooper, Adam Denes, Bart J. L. Eggen, Ukpong Eyo, Elena Galea, Sonia Garel, Florent Ginhoux, Christopher K. Glass, Ozgun Gokce, Diego Gomez-Nicola, Berta Gonzalez, Siamon Gordon, Manuel B. Graeber, Andrew D. Greenhalgh, Pierre Gressens, Melanie Greter, David H. Gutmann, Christian Haass, Michael T. Heneka, Frank L. Heppner, Soyon Hong, David A. Hume, Steffen Jung, Helmut Kettenmann, Jonathan Kipnis, Ryuta Koyama, Greg Lemke, Marina Lynch, Ania Majewska, Marzia Malcangio, Tarja Malm, Renzo Mancuso, Takahiro Masuda, Michela Matteoli, Barry W. McColl, Veronique E. Miron, Anna Victoria Molofsky, Michelle Monje, Eva Mracsko, Agnes Nadjar, Jonas J. Neher, Urte Neniskyte, Harald Neumann, Mami Noda, Bo Peng, Francesca Peri, V. Hugh Perry, Phillip G. Popovich, Clare Pridans, Josef Priller, Marco Prinz, Davide Ragozzino, Richard M. Ransohoff, Michael W. Salter, Anne Schaefer, Dorothy P. Schafer, Michal Schwartz, Mikael Simons, Cody J. Smith, Wolfgang J. Streit, Tuan Leng Tay, Li-Huei Tsai, Alexei Verkhratsky, Rommy von Bernhardi, Hiroaki Wake, Valerie Wittamer, Susanne A. Wolf, Long-Jun Wu, Tony Wyss-Coray
Summary: Microglial research has made significant progress, but the current classification system fails to accurately describe their diversity, leading to misconceptions about their functions. To address this issue, a group of multidisciplinary experts has proposed a naming framework and recommendations to help researchers better understand and describe the different states and functions of microglia.
Meeting Abstract
Clinical Neurology
Emily Hansen, Anna S. Warden, Cristina Mora, Gabriela Ramirez, Samantha Mak, Sanjana Narayan, Samantha Trescott, Shreya Shriram, Zahara Keulen, Christopher K. Glass, Nicole G. Coufal
ANNALS OF NEUROLOGY
(2022)
