The role of NLRP3-CASP1 in inflammasome-mediated neuroinflammation and autophagy dysfunction in manganese-induced, hippocampal-dependent impairment of learning and memory ability
Diya Wang,Jianbin Zhang,Wenkai Jiang,Zipeng Cao,Fang Zhao,Tongjian Cai,Michael Aschner,Wenjing Luo +7 more
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TLDR
It is demonstrated that Mn activates the NLRP3-CASP1 inflammasome pathway in the hippocampus of mice and BV2 cells by triggering autophagy-lysosomal dysfunction, leading to hippocampal-dependent impairment in learning and memory, which is associated with the pathogenesis of Alzheimer disease.Abstract:
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. We demonstrate that Mn activates the NLRP3-CASP1 inflammasome pathway in the hippocampus of mice and BV2 cells by triggering autophagy-lysosomal dysfunction. The autophagy-lysosomal dysfunction is induced by lysosomal damage caused by excessive Mn accumulation, damaging the structure and normal function of these organelles. Additionally, we show that the release of lysosomal CTSB (cathepsin B) plays an important role in Mn-induced NLRP3-CASP1 inflammasome activation, and that the increased autophagosomes in the cytoplasm are not the main cause of NLRP3-CASP1 inflammasome activation. The accumulation of proinflammatory cytokines, such as IL1B (interleukin 1 β) and IL18 (interleukin 18), as well as the dysfunctional autophagy pathway may damage hippocampal neuronal cells, thus leading to hippocampal-dependent impairment in learning and memory, which is associated with the pathogenesis of Alzheimer disease (AD).read more
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Metal Toxicity Links to Alzheimer's Disease and Neuroinflammation.
Tee Jong Huat,Judith Camats-Perna,Estella A. Newcombe,Nicholas Valmas,Masashi Kitazawa,Rodrigo Medeiros +5 more
TL;DR: How metals affect brain physiology and immunity, as well as their roles in the accumulation of toxic AD proteinaceous species (i.e., β-amyloid and tau) are reviewed to increase the awareness of metals as players in the onset and progression of AD.
Guidelines for the use and interpretatoin of assays for monitoring autophagy
D. J. Klionsky,F. C. Abdalla,H. Abeliovich,R. T. Abraham,A. Acevedo-Arozena,K. Adeli,L. Agholme,M. Agnello,A. M. Engelbrecht,B. Loos +9 more
TL;DR: In this paper, the authors present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macro-autophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes.
Journal ArticleDOI
Beclin1-driven autophagy modulates the inflammatory response of microglia via NLRP3
Judith Houtman,Kiara Freitag,Kiara Freitag,Niclas Gimber,Jan Schmoranzer,Frank L. Heppner,Frank L. Heppner,Marina Jendrach +7 more
TL;DR: The notion that selective autophagy can impact microglia activation by modulating IL‐1beta and IL‐18 production via NLRP3 degradation is supported and the mechanism how impaired autophagic could contribute to neuroinflammation in Alzheimer's disease is presented.
Journal ArticleDOI
Melatonin prevents neuroinflammation and relieves depression by attenuating autophagy impairment through FOXO3a regulation.
Tahir Ali,Shafiq Ur Rahman,Shafiq Ur Rahman,Qiang Hao,Weifen Li,Zizhen Liu,Fawad Ali Shah,Fawad Ali Shah,Iram Murtaza,Zaijun Zhang,Xifei Yang,Gong-Ping Liu,Gong-Ping Liu,Shupeng Li,Shupeng Li +14 more
TL;DR: The present study concludes that the anti-depressive effects of melatonin in LPS-induced depression might be mediated via autophagy modulation through FOXO3a signaling.
Journal ArticleDOI
The role of lysosomal cysteine cathepsins in NLRP3 inflammasome activation.
Rhiannon I. Campden,Yifei Zhang +1 more
TL;DR: Lysosomal cysteine cathepsins are members of a diverse and complementary family, and likely share both overlapping and independent functions in NLRP3 inflammasome activation.
References
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Platanias,Stefanie Pöggeler,Marc Poirot,Angelo Poletti,Christian Poüs,Mercedes Pozuelo-Rubio,Mette Prætorius-Ibba,Anil Prasad,Mark Prescott,Muriel Priault,Nathalie Produit-Zengaffinen,Ann Progulske-Fox,Tassula Proikas-Cezanne,Serge Przedborski,Karin Przyklenk,Rosa Puertollano,Julien Puyal,Shu-Bing Qian,Liang Qin,Zheng-Hong Qin,Susan E. Quaggin,Nina Raben,Hannah Rabinowich,Simon W. Rabkin,Irfan Rahman,Abdelhaq Rami,Georg Ramm,Glenn Randall,Felix Randow,V. Ashutosh Rao,Jeffrey C. Rathmell,Brinda Ravikumar,Swapan K. Ray,Bruce H. Reed,John C. Reed,Fulvio Reggiori,Anne Régnier-Vigouroux,Anne Régnier-Vigouroux,Andreas S. Reichert,John J. Reiners,Russel J. Reiter,Jun Ren,José L. Revuelta,Christopher J. Rhodes,Konstantinos Ritis,Elizete Rizzo,Jeffrey Robbins,Michel Roberge,Hernan Roca,Maria Carmela Roccheri,Stéphane Rocchi,H. Peter Rodemann,Santiago Rodríguez de Córdoba,Bärbel Rohrer,Igor B. Roninson,Kirill V. Rosen,Magdalena Rost-Roszkowska,Mustapha Rouis,Kasper M.A. Rouschop,Francesca Rovetta,Brian P. Rubin,David C. Rubinsztein,Klaus Ruckdeschel,Edmund B. Rucker,Assaf Rudich,Emil Rudolf,Nelson Ruiz-Opazo,Rossella Russo,Tor Erik Rusten,Kevin M. Ryan,Stefan W. Ryter,David M. Sabatini,Junichi Sadoshima,Tapas Saha,Tatsuya Saitoh,Hiroshi Sakagami,Yasuyoshi Sakai,Ghasem Hosseini Salekdeh,Paolo Salomoni,Paul M. Salvaterra,Guy S. Salvesen,Rosa Salvioli,Anthony Sanchez,José Antonio Sánchez-Alcázar,Ricardo Sánchez-Prieto,Marco Sandri,Uma Sankar,Poonam Sansanwal,Laura Santambrogio,Shweta Saran,Sovan Sarkar,Minnie M. Sarwal,Chihiro Sasakawa,Ausra Sasnauskiene,Miklós Sass,Ken Sato,Miyuki Sato,Anthony H.V. Schapira,Michael Scharl,Hermann M. Schätzl,Wiep Scheper,Stefano Schiaffino,Claudio Schneider,Marion Schneider,Regine Schneider-Stock,Patricia V. Schoenlein,Daniel F. Schorderet,Christoph Schüller,Gary K. Schwartz,Luca Scorrano,Linda Sealy,Per Ottar Seglen,Juan Segura-Aguilar,Iban Seiliez,Oleksandr Seleverstov,Christian Sell,Jong Bok Seo,Duska Separovic,Vijayasaradhi Setaluri,Takao Setoguchi,Carmine Settembre,John J. Shacka,Mala Shanmugam,Irving M. Shapiro,Eitan Shaulian,Reuben J. Shaw,James H. Shelhamer,Han-Ming Shen,Wei-Chiang Shen,Zu-Hang Sheng,Yang Shi,Kenichi Shibuya,Yoshihiro Shidoji,Jeng-Jer Shieh,Chwen Ming Shih,Yohta Shimada,Shigeomi Shimizu,Takahiro Shintani,Orian S. Shirihai,Gordon C. Shore,Andriy A. Sibirny,Andriy A. Sibirny,Stan B. Sidhu,Beata Sikorska,Elaine C.M. Silva-Zacarin,Alison Simmons,Anna Katharina Simon,Hans-Uwe Simon,Cristiano Simone,Anne Simonsen,David A. Sinclair,Rajat Singh,Debasish Sinha,Frank A. Sinicrope,Agnieszka Sirko,Parco M. Siu,Efthimios Sivridis,Vojtech Skop,Vladimir P. Skulachev,Ruth S. Slack,Soraya S. Smaili,Duncan R. Smith,Maria S. Soengas,Thierry Soldati,Xueqin Song,Anil K. Sood,Tuck Wah Soong,Federica Sotgia,Stephen A. Spector,Stephen A. Spector,Claudia Spies,Wolfdieter Springer,Srinivasa M. Srinivasula,Leonidas Stefanis,Joan S. Steffan,Ruediger Stendel,Harald Stenmark,Anastasis Stephanou,Stephan T. Stern,Cinthya Sternberg,Björn Stork,Peter Strålfors,Carlos S. Subauste,Xinbing Sui,David Sulzer,Jiaren Sun,Shi-Yong Sun,Zhi Jun Sun,Joseph J.Y. Sung,Kuninori Suzuki,Toshihiko Suzuki,Michele S. Swanson,Charles Swanton,Sean T. Sweeney,Lai King Sy,Gyorgy Szabadkai,Ira Tabas,Heinrich Taegtmeyer,Marco Tafani,Krisztina Takács-Vellai,Yoshitaka Takano,Kaoru Takegawa,Genzou Takemura,Fumihiko Takeshita,Nicholas J. Talbot,Kevin S. W. Tan,Keiji Tanaka,Kozo Tanaka,Daolin Tang,Dingzhong Tang,Isei Tanida,Bakhos A. Tannous,Nektarios Tavernarakis,Graham S. Taylor,Gregory A. Taylor,J. Paul Taylor,Ance S. Terada,Alexei Terman,Gianluca Tettamanti,Karin Thevissen,Craig B. Thompson,Andrew Thorburn,Michael Thumm,Feng Feng Tian,Yuan Tian,Glauco P. Tocchini-Valentini,Aviva M. Tolkovsky,Yasuhiko Tomino,Lars Tönges,Sharon A. Tooze,Cathy Tournier,John Tower,Roberto Towns,Vladimir Trajkovic,Leonardo H. Travassos,Ting Fen Tsai,Mario P. Tschan,Takeshi Tsubata,Allan Tsung,Boris Turk,Lorianne S. Turner,Suresh C. Tyagi,Yasuo Uchiyama,Takashi Ueno,Midori Umekawa,Rika Umemiya-Shirafuji,Vivek K. Unni,Maria I. Vaccaro,Enza Maria Valente,Enza Maria Valente,Greet Van den Berghe,Ida J. van der Klei,Wouter G. van Doorn,Linda F. van Dyk,Marjolein van Egmond,Leo A. van Grunsven,Peter Vandenabeele,Wim Vandenberghe,Ilse Vanhorebeek,Eva C. Vaquero,Guillermo Velasco,Tibor Vellai,Jose Miguel Vicencio,Richard D. Vierstra,Miquel Vila,Cécile Vindis,Cécile Vindis,Giampietro Viola,Maria Teresa Viscomi,Olga V. Voitsekhovskaja,Clarissa von Haefen,Marcela Votruba,Keiji Wada,Richard Wade-Martins,Cheryl L. Walker,Craig M. Walsh,Jochen Walter,Xiang Bo Wan,Aimin Wang,Chenguang Wang,Dawei Wang,Fan Wang,Fen Wang,Guanghui Wang,Haichao Wang,Hong Gang Wang,Horng-Dar Wang,Jin Wang,Ke Wang,Mei Wang,Richard C. Wang,Xinglong Wang,Xuejun Wang,Ying Jan Wang,Yipeng Wang,Zhen Wang,Zhigang Charles Wang,Zhi-Nong Wang,Derick G. Wansink,Diane M. Ward,Hirotaka Watada,Sarah Waters,Paul Webster,Lixin Wei,Conrad C. Weihl,William A. Weiss,Scott M. Welford,Longping Wen,Caroline A. Whitehouse,J. Lindsay Whitton,Alexander J. Whitworth,Thomas Wileman,John W. Wiley,Simon Wilkinson,Dieter Willbold,Roger L. Williams,Peter R. Williamson,Bradly G. Wouters,Chenghan Wu,Dao Cheng Wu,William K.K. Wu,Andreas Wyttenbach,Ramnik J. Xavier,Zhijun Xi,Pu Xia,Gengfu Xiao,Zhiping Xie,Zhonglin Xie,Da Zhi Xu,Jianzhen Xu,Liang Xu,Xiaolei Xu,Ai Yamamoto,Akitsugu Yamamoto,Shunhei Yamashina,Michiaki Yamashita,Xianghua Yan,Mitsuhiro Yanagida,Dun-Sheng Yang,Elizabeth Yang,Jin Ming Yang,Shi Yu Yang,Wannian Yang,Wei Yuan Yang,Zhifen Yang,Meng-Chao Yao,Tso-Pang Yao,Behzad Yeganeh,Wei Lien Yen,Jia Jing Yin,Xiao Ming Yin,Ook Joon Yoo,Gyesoon Yoon,Seung Yong Yoon,Tomohiro Yorimitsu,Yuko Yoshikawa,Tamotsu Yoshimori,Kohki Yoshimoto,Ho Jin You,Richard J. Youle,Anas Younes,Li Yu,Long Yu,Seong-Woon Yu,Wai Haung Yu,Zhi-Min Yuan,Zhenyu Yue,Cheol-Heui Yun,Michisuke Yuzaki,Olga Zabirnyk,Elaine Silva-Zacarin,E. David Zacks,Ldad Zacksenhaus,Nadia Zaffaroni,Zahra Zakeri,Herbert J. Zeh,Scott Zeitlin,Hong Zhang,Hui Ling Zhang,Jianhua Zhang,Jing Pu Zhang,Lin Zhang,Long Zhang,Ming Yong Zhang,Xudong Zhang,Mantong Zhao,Yi Fang Zhao,Ying Zhao,Zhizhuang J. Zhao,Xiaoxiang Zheng,Boris Zhivotovsky,Qing Zhong,Cong Zhao Zhou,Changlian Zhu,Wei-Guo Zhu,Xiao Feng Zhu,Xiongwei Zhu,Yuangang Zhu,Teresa Zoladek,Wei-Xing Zong,Antonio Zorzano,Jürgen Zschocke,Brian S. Zuckerbraun +1287 more
TL;DR: These guidelines are presented for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes.
Journal ArticleDOI
Methods in Mammalian Autophagy Research
TL;DR: Methods to monitor autophagy and to modulate autophagic activity are discussed, with a primary focus on mammalian macroautophagy.
Journal ArticleDOI
Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization
Veit Hornung,Franz Bauernfeind,Annett Halle,Eivind O. Samstad,Eivind O. Samstad,Hajime Kono,Kenneth L. Rock,Katherine A. Fitzgerald,Eicke Latz,Eicke Latz +9 more
TL;DR: It is demonstrated that silica and aluminum salt crystals activated inflammasomes formed by the cytoplasmic receptor NALP3, which senses lysosomal damage as an endogenous 'danger' signal.