Article
Biology
Willa Wen-You Yim, Hayashi Yamamoto, Noboru Mizushima
Summary: Monitoring autophagic flux is crucial for autophagy studies. Current assays for mammalian cells are complicated and yield less accurate results. This paper presents a HaloTag-based processing assay to monitor autophagic flux in mammalian cells, which provides a simple and effective method for precise measurement.
Article
Cell Biology
Takeshi Yamamoto, Yoshitsugu Takabatake, Satoshi Minami, Shinsuke Sakai, Ryuta Fujimura, Atsushi Takahashi, Tomoko Namba-Hamano, Jun Matsuda, Tomonori Kimura, Isao Matsui, Jun-Ya Kaimori, Hiroaki Takeda, Masatomo Takahashi, Yoshihiro Izumi, Takeshi Bamba, Taiji Matsusaka, Fumio Niimura, Motoko Yanagita, Yoshitaka Isaka
Summary: The study found that supplementation with EPA can alleviate renal lipotoxicity by reducing phospholipid accumulation in lysosomes, improving mitochondrial dysfunction, reducing inflammation and fibrosis. EPA alleviates renal lipotoxicity by improving lysosomal function and autophagic flux in both high-fat diet-fed mice and isolated PTECs cultured in palmitic acid, indicating its potential as a novel treatment for obesity-related kidney diseases.
Article
Multidisciplinary Sciences
Shi Tai, Jiaxing Sun, Yuying Zhou, Zhaowei Zhu, Yuhu He, Mingxian Chen, Hui Yang, Yichao Xiao, Tao Tu, Liang Tang, Xuping Li, Jianping Zeng, Xilong Zheng, Shenghua Zhou
Summary: In this study, it was found that metformin prevents VSMC and vascular senescence by promoting autolysosome formation. Specifically, metformin enhanced the autophagic flux at the autophagosome-lysosome fusion level, thereby inhibiting Ang II-induced cellular and vascular senescence.
JOURNAL OF ADVANCED RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Doudou Luo, Wenxuan Ye, Ling Chen, Xiaoqian Yuan, Yali Zhang, Caixia Chen, Xin Jin, Yu Zhou
Summary: Astrocyte inflammation activation hinders motor function recovery after cerebral ischemia, and the molecular mechanism is not clearly understood. This study investigates the role of PPARa in astrocyte inflammation activation after cerebral ischemia and explores the underlying mechanism. The results show that PPARa dysfunction promotes astrocyte inflammatory activation, while PPARa activation preserves lysosome function and restores autophagic flux in astrocytes after oxygen-glucose deprivation/reoxygenation (OGD/R).
Article
Neurosciences
Lisa Gallwitz, Lina Schmidt, Andre R. A. Marques, Andreas Tholey, Liam Cassidy, Irem Ulku, Gerhard Multhaup, Alessandro Di Spiezio, Paul Saftig
Summary: CTSD has proteolytic cleavage activity on human Aβ1-42, but does not play a prominent role in APP processing and Aβ degradation.
NEUROBIOLOGY OF DISEASE
(2022)
Editorial Material
Cell Biology
Willa Wen-You Yim, Hayashi Yamamoto, Noboru Mizushima
Summary: This article discusses a HaloTag-based method for monitoring autophagic flux. The fusion of HaloTag with the autophagy protein LC3 allows for complete degradation of the reporter in lysosomes. However, when labeled with the HaloTag ligand, free HaloTag ligand is released upon processing by lysosomal enzymes. The quantifiable amount of free HaloTag ligand, detected through immunoblotting or in-gel fluorescence, reflects autophagic flux.
Article
Cell Biology
Aleksandra Hac, Karolina Pierzynowska, Anna Herman-Antosiewicz
Summary: S6K1 plays a crucial role in autophagy by controlling tubulin acetylation, thereby influencing autophagic flux; the absence of S6K1 disrupts acetylated microtubule network, impairing fusion between autophagosomes and lysosomes.
Article
Neurosciences
Ki-Ryeong Kim, Sang Eun Park, Ji-Ye Hong, Jae-Young Koh, Dong-Hyung Cho, Jung Jin Hwang, Yang-Hee Kim
Summary: This study reveals that zinc can activate autophagy and lysosomes, promoting the treatment of neurodegenerative diseases through the regulation of transcription factor EB and V-ATPase. Zinc activates lysosomal proteases and lysosomal acidification, reducing protein aggregation and phosphorylation of tau protein, demonstrating its potential therapeutic effect.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Pharmacology & Pharmacy
Xin He, Wei Yuan, Fei Liu, Juan Feng, Yanxia Guo
Summary: This study demonstrates the neuroprotective effects of ghrelin in 6-OHDA-induced PD models by improving autophagic flux dysfunction and restoring TFEB level. This effect is achieved through regulating the expression of autophagy-related proteins, increasing cell viability, and reducing the levels of apoptosis-related proteins.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Yoshinori Tanaka, Shun-ya Kusumoto, Yuki Honma, Kosuke Takeya, Masumi Eto
Summary: In this study, we found that PGRN overexpression suppresses autophagic flux and worsens the pathology of neurodegenerative diseases.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Chemistry, Medicinal
Li Luo, Yonghong Liang, Yuanyuan Fu, Zhiyuan Liang, Jinfen Zheng, Jie Lan, Feihai Shen, Zhiying Huang
Summary: In this study, the hepatotoxicity of TSN was investigated both in vivo and in vitro. TSN was found to induce upregulation of autophagy-marker proteins and accumulation of autolysosomes, resulting in the inhibition of autophagic flux. It was also shown that TSN affected the acidity and degradation capacity of lysosomes, as well as the expression of hydrolase cathepsin B. The inhibition of transcription factor EB (TFEB) played a key role in TSN-induced hepatotoxicity. Activation of autophagy alleviated TSN-induced hepatocyte damage.
Review
Cell Biology
Randini Nanayakkara, Rajendra Gurung, Samuel J. J. Rodgers, Matthew J. J. Eramo, Georg Ramm, Christina A. A. Mitchell, Meagan J. J. McGrath
Summary: This review provides an overview of the importance of lysosome reformation in maintaining autophagy function and the role of ALR dysfunction in various diseases.
Article
Environmental Sciences
Yan Wang, Ying Ma, Yongshuai Yao, Qing Liu, Yanting Pang, Meng Tang
Summary: This study assessed the dynamic autophagic state in human vascular endothelial cells exposed to ambient particulate matter by detecting autophagic marker proteins and turnover assays. The results showed that PM SRM1648a can induce excess autophagic vacuoles in cells, with differences in underlying causes based on exposure duration. It was found that LC3II upregulation was due to intensifying autophagic initiation after 6 hours of exposure, while longer exposure periods resulted in defective autophagy and lysosomal dysfunction.
ENVIRONMENTAL POLLUTION
(2021)
Review
Pharmacology & Pharmacy
Olja Mijanovic, Anastasiia I. Petushkova, Ana Brankovic, Boris Turk, Anna B. Solovieva, Angelina I. Nikitkina, Sergey Bolevich, Peter S. Timashev, Alessandro Parodi, Andrey A. Zamyatnin
Summary: Lysosomal proteases, specifically human cathepsin D, play a crucial role in maintaining cell homeostasis by managing protein turnover. Dysregulation of cathepsin D can contribute to various disorders, such as neurodegenerative diseases and cancer progression. Targeting cathepsin D could provide significant diagnostic benefits and innovative therapeutic approaches.
Article
Cell Biology
Alessandra Romagnoli, Martina Di Rienzo, Elisa Petruccioli, Carmela Fusco, Ivana Palucci, Lucia Micale, Tommaso Mazza, Giovanni Delogu, Giuseppe Merla, Delia Goletti, Mauro Piacentini, Gian Maria Fimia
Summary: In this study, the role of TRIM proteins in the host response to Mtb infection was investigated. TRIM32 was identified as a novel factor involved in the intracellular response to Mtb infection, promoting autophagy-mediated Mtb degradation. Silencing TRIM32 expression in THP1 cells resulted in increased intracellular growth of Mtb, impaired Mtb ubiquitination, reduced recruitment of autophagy proteins to Mtb, and decreased autophagosome formation. These findings suggest that TRIM32 plays an important role in the host response to Mtb infection and could be a promising target for tuberculosis therapies.
CELL DEATH & DISEASE
(2023)
Article
Endocrinology & Metabolism
Jianmin Zhang, Jia Yang, Huaishan Wang, Omar Sherbini, Matthew J. Keuss, George K. E. Umanah, Emily Ling-Lin Pai, Zhikai Chi, Kaisa M. A. Paldanius, Wei He, Hong Wang, Shaida A. Andrabi, Ted M. Dawson, Valina L. Dawson
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2019)
Article
Pharmacology & Pharmacy
Mohammed Hossain, Joshua M. Marcus, Jun Hee Lee, Patrick L. Garcia, Jean-Philippe Gagne, Guy G. Poirier, Charles N. Falany, Shaida A. Andrabi
DRUG METABOLISM AND DISPOSITION
(2019)
Article
Biochemistry & Molecular Biology
Linlin Gu, Jennifer L. Larson Casey, Shaida A. Andrabi, Jun Hee Lee, Selene Meza-Perez, Troy D. Randall, A. Brent Carter
Article
Multidisciplinary Sciences
Changzhao Li, Bharat Mishra, Mahendra Kashyap, Zhiping Weng, Shaida A. Andrabi, Shahid M. Mukhtar, Arianna L. Kim, David R. Bickers, Levy Kopelovich, Mohammad Athar
SCIENTIFIC REPORTS
(2019)
Article
Multidisciplinary Sciences
Ank Agarwal, Seongje Park, Shinwon Ha, Ji-Sun Kwon, Mohammed Repon Khan, Bong Gu Kang, Ted M. Dawson, Valina L. Dawson, Shaida A. Andrabi, Sung-Ung Kang
Article
Cell & Tissue Engineering
Manoj Kumar, Jesus Acevedo-Cintron, Aanishaa Jhaldiyal, Hu Wang, Shaida A. Andrabi, Stephen Eacker, Senthilkumar S. Karuppagounder, Saurav Brahmachari, Rong Chen, Hyesoo Kim, Han Seok Ko, Valina L. Dawson, Ted M. Dawson
Review
Pharmacology & Pharmacy
Mudasir S. Andrabi, Shaida A. Andrabi
FRONTIERS IN PHARMACOLOGY
(2020)
Article
Biochemistry & Molecular Biology
Joshua M. Marcus, Mohammed I. Hossain, Jean-Philippe Gagne, Guy G. Poirier, Lori L. McMahon, Rita M. Cowell, Shaida A. Andrabi
Summary: This study revealed that the cytosolic translocation of TDP-43 in neurodegenerative disease depends on activation of PARP-1, and suggested that PARP inhibitors could have a neuroprotective role in diseases involving TDP-43.
NEUROCHEMISTRY INTERNATIONAL
(2021)
Article
Cell Biology
Areum Jo, Yunjong Lee, Tae-In Kam, Sung-Ung Kang, Stewart Neifert, Senthilkumar S. Karuppagounder, Rin Khang, Hojin Kang, Hyejin Park, Shih-Ching Chou, Sungtaek Oh, Haisong Jiang, Deborah A. Swing, Sangwoo Ham, Sheila Pirooznia, George K. E. Umanah, Xiaobo Mao, Manoj Kumar, Han Seok Ko, Ho Chul Kang, Byoung Dae Lee, Yun-Il Lee, Shaida A. Andrabi, Chi-Hu Park, Ji-Yeong Lee, Hanna Kim, Hyein Kim, Hyojung Kim, Jin Whan Cho, Sun Ha Paek, Chan Hyun Na, Lino Tessarollo, Valina L. Dawson, Ted M. Dawson, Joo-Ho Shin
Summary: Accumulation of parkin-interacting substrate (PARIS) due to inactivation of parkin contributes to Parkinson's disease (PD) through repression of peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1 alpha) activity. Farnesol, identified as an inhibitor of PARIS, promotes farnesylation of PARIS and prevents its repression of PGC-1 alpha by reducing PARIS occupancy on the PPARGC1A promoter. Studies show that farnesol can prevent dopaminergic neuronal loss and behavioral deficits by enhancing PARIS farnesylation, suggesting a potential therapeutic role in PD treatment.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Article
Cell Biology
Jun Wang, Holly R. Thomas, Zhang Li, Nan Cher (Florence) Yeo, Hannah E. Scott, Nghi Dang, Mohammed Iqbal Hossain, Shaida A. Andrabi, John M. Parant
Summary: Cellular stress can lead to human disease pathologies due to aberrant cell death. The study found both common and unique molecular pathways involved in different stress responses, with p53 and puma playing key roles. The data suggests that Puma may be the key mediator of p53-dependent apoptosis, and inhibitors targeting Puma could have therapeutic applications.
CELL DEATH & DISEASE
(2021)
Correction
Multidisciplinary Sciences
Changzhao Li, Bharat Mishra, Mahendra Kashyap, Zhiping Weng, Shaida A. Andrabi, Shahid M. Mukhtar, Arianna L. Kim, David R. Bickers, Levy Kopelovich, Mohammad Athar
SCIENTIFIC REPORTS
(2021)
Correction
Oncology
Debangshu Samanta, Youngrok Park, Shaida A. Andrabi, Laura M. Shelton, Daniele M. Gilkes, Gregg L. Semenza
Article
Multidisciplinary Sciences
Alan Umfress, Ayanabha Chakraborti, Suma Priya Sudarsana Devi, Raegan Adams, Daniel Epstein, Adriana Massicano, Anna Sorace, Sarbjit Singh, M. Iqbal Hossian, Shaida A. Andrabi, David K. Crossman, Nilesh Kumar, M. Shahid Mukhtar, Huiyang Luo, Claire Simpson, Kathryn Abell, Matthew Stokes, Thorsten Wiederhold, Charles Rosen, Hongbing Lu, Amarnath Natarajan, James A. Bibb
Summary: Millions of traumatic brain injuries (TBIs) occur annually, commonly resulting from falls, traffic accidents, and sports-related injuries involving rotational acceleration/deceleration of the brain. This study developed a new model of repetitive rotational head trauma in rodents and demonstrated acute and prolonged pathological, behavioral, and electrophysiological effects of rotational TBI (rTBI). The aberrant activity of Cyclin-dependent kinase 5 (Cdk5) was identified as a principal mediator of rTBI, and pharmacological inhibition of Cdk5 showed promising results in reducing the cognitive and pathological consequences of injury.
SCIENTIFIC REPORTS
(2023)
Article
Cell Biology
George K. E. Umanah, Mehdi Ghasemi, Xiling Yin, Melissa Chang, Jin Wan Kim, Jianmin Zhang, Erica Ma, Leslie A. Scarffe, Yun-Il Lee, Rong Chen, Kavya Tangella, Amy McNamara, Leire Abalde-Atristain, Mohamad A. Dar, Samuel Bennett, Marisol Cortes, Shaida A. Andrabi, Paschalis-Thomas Doulias, Harry Ischiropoulos, Ted M. Dawson, Valina L. Dawson