Article
Clinical Neurology
Hadjara Sidibe, Yousra Khalfallah, Shangxi Xiao, Nicolas B. Gomez, Hana Fakim, Elizabeth M. H. Tank, Genevieve Di Tomasso, Eric Bareke, Anais Aulas, Paul M. McKeever, Ze'ev Melamed, Laurie Destroimaisons, Jade-Emmanuelle Deshaies, Lorne Zinman, J. Alex Parker, Pascale Legault, Martine Tetreault, Sami J. Barmada, Janice Robertson, Christine Vande Velde
Summary: The study reveals that TDP-43 stabilizes G3BP1 transcripts, nuclear TDP-43 depletion is sufficient to reduce G3BP1 protein levels, and G3BP1 transcripts are reduced in neurons of ALS/FTD patients with TDP-43 cytoplasmic inclusions/nuclear depletion. These findings suggest that loss of function of TDP-43 and G3BP1 may contribute to ALS/FTD pathogenesis.
Article
Biochemistry & Molecular Biology
Giada Zanini, Valentina Selleri, Milena Nasi, Anna De Gaetano, Ilaria Martinelli, Giulia Gianferrari, Francesco Demetrio Lofaro, Federica Boraldi, Jessica Mandrioli, Marcello Pinti
Summary: This study reports the clinical and biological features of an ALS patient with pA382T mutation in TPD-43 protein. The mutation leads to significant alterations in neuronal proteome, particularly impacting mitochondrial metabolic pathways and the endoplasmic reticulum. The findings suggest that mitochondrial dysfunction and misplacement of mitochondrial DNA may be mechanisms contributing to ALS caused by this mutation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Clinical Neurology
Lindsey R. Hayes, Petr Kalab
Summary: Nuclear clearance and cytoplasmic mislocalization of TDP-43 protein are pathological features of neurodegenerative disorders. The mislocalization of TDP-43 leads to neurodegeneration through disruption of RNA processing and cellular functions. Therapies for TDP-43 primarily focus on clearing TDP-43 aggregates, and future strategies aim to address the upstream causes of TDP-43 disruption.
Article
Biochemistry & Molecular Biology
Nikolina Prtenjaca, Matea Rob, Muhammad S. Alam, Andrea Markovinovic, Cristiana Stuani, Emanuele Buratti, Ivana Munitic
Summary: Deficiency of optineurin protein leads to upregulation of TDP-43 protein expression in microglial cells, and this upregulation is not affected by inflammatory stimuli. This finding is important for understanding the pathogenesis of ALS.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Clinical Neurology
Fumiaki Mori, Hina Yasui, Yasuo Miki, Tomoya Kon, Akira Arai, Hidekachi Kurotaki, Masahiko Tomiyama, Koichi Wakabayashi
Summary: This study found that TDP-43 and SGs colocalize at the early stage of TDP-43 aggregation, suggesting the involvement of SGs in the formation of TDP-43 inclusions.
Article
Clinical Neurology
Yuting Ren, Siyuan Li, Siyu Chen, Xiaosun Sun, Fei Yang, Hongfen Wang, Mao Li, Fang Cui, Xusheng Huang
Summary: The levels of plasma TDP-43 and pTDP-43 were significantly higher in ALS patients compared to healthy controls, with plasma TDP-43 showing high sensitivity and specificity in differentiating between the two groups and indicating disease progression.
FRONTIERS IN NEUROLOGY
(2021)
Article
Cell Biology
Naomi Hartopp, Dawn H. W. Lau, Sandra M. Martin-Guerrero, Andrea Markovinovic, Gabor M. Morotz, Jenny Greig, Elizabeth B. Glennon, Claire Troakes, Patricia Gomez-Suaga, Wendy Noble, Christopher C. J. Miller
Summary: This study investigates the alterations in VAPB-PTPIP51 tethers in the spinal cords of ALS patients and healthy individuals. The findings show a reduction in VAPB protein levels and disrupted VAPB-PTPIP51 tethers in ALS patients.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Hei W. A. Cheng, Timothy B. Callis, Andrew P. Montgomery, Jonathan J. Danon, William T. Jorgensen, Yazi D. Ke, Lars M. Ittner, Eryn L. Werry, Michael Kassiou
Summary: The use of cellular models in drug discovery for ALS and FTD is common, but there is currently no consensus on the most accurate model to replicate key pathological features. This study characterized two TDP-43 proteinopathy cellular models and found that different effects were observed when small molecule probes were exposed to these models. The study highlights the challenges of using cellular models in lead development and emphasizes the need for evaluations of novel therapeutics across various cell lines and aetiological models.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Clinical Neurology
Tomoya Kon, Fumiaki Mori, Kunikazu Tanji, Yasuo Miki, Haruo Nishijima, Takashi Nakamura, Iku Kinoshita, Chieko Suzuki, Hidekachi Kurotaki, Masahiko Tomiyama, Koichi Wakabayashi
Summary: DPCS is the primary manifestation of short-duration ALS, with a high density and an inverse correlation with disease duration. DPCS is associated with nonfibrillar TDP-43 localized to the ribosomes of the rough endoplasmic reticulum.
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
(2022)
Article
Geriatrics & Gerontology
Zhe Long, Muireann Irish, John R. Hodges, Glenda Halliday, Olivier Piguet, James R. Burrell
Summary: Clinical and pathological heterogeneity is common in patients with frontotemporal lobar degeneration (FTLD) pathology. Characteristics that differentiate between FTLD-TDP and FTLD-tau, as well as different subtypes within FTLD-TDP, were investigated. Amyotrophic lateral sclerosis features were highly specific for FTLD-TDP, which showed greater atrophy than FTLD-tau. TDP-43 subtyping may have more clinical utility in distinguishing different profiles within FTLD-TDP.
NEUROBIOLOGY OF AGING
(2021)
Review
Neurosciences
Sarah Lepine, Maria Jose Castellanos-Montiel, Thomas Martin Durcan
Summary: The abnormal synaptic function of TDP-43 is closely related to NMJ disruption in ALS, and it may exert its effects by influencing molecular mechanisms within motor neurons, skeletal muscles, and glial cells.
TRANSLATIONAL NEURODEGENERATION
(2022)
Article
Neurosciences
Maize C. Cao, Brigid Ryan, Jane Wu, Maurice A. Curtis, Richard L. M. Faull, Mike Dragunow, Emma L. Scotter
Summary: TDP-43 dysfunction is a molecular characteristic of ALS and FTD. It leads to the loss of normal nuclear function, resulting in impaired RNA regulation and the emergence of cryptic exons. Cryptic exons and differential exon usage are promising markers of TDP-43 dysfunction in ALS/FTD and provide insights into neurodegenerative pathways.
NEUROBIOLOGY OF DISEASE
(2023)
Article
Neurosciences
Molly E. V. Swanson, Miran Mrkela, Helen C. C. Murray, Maize C. C. Cao, Clinton Turner, Maurice A. A. Curtis, Richard L. M. Faull, Adam K. K. Walker, Emma L. L. Scotter
Summary: The activation of microglia in ALS is associated with TDP-43 aggregation, with phagocytic state in early-stage disease and dysfunctional state in end-stage disease. These findings enhance our understanding of microglial phenotypes and function in ALS.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2023)
Article
Neurosciences
Emily E. Handley, Laura A. Reale, Jyoti A. Chuckowree, Marcus S. Dyer, Grace L. Barnett, Courtney M. Clark, William Bennett, Tracey C. Dickson, Catherine A. Blizzard
Summary: Estrogen plays a significant role in mitigating disease progression and pathogenesis in ALS, by influencing spine density and plasticity, resulting in improved disease severity and outcomes.
MOLECULAR NEUROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Greta Grassmann, Mattia Miotto, Lorenzo Di Rienzo, Federico Salaris, Beatrice Silvestri, Elsa Zacco, Alessandro Rosa, Gian Gaetano Tartaglia, Giancarlo Ruocco, Edoardo Milanetti
Summary: This article investigates the protein aggregation process in ALS, providing a computational model of interaction based on the evaluation of shape complementarity at the molecular interfaces. The study proposes and assesses possible association mechanisms between CTFs, and performs molecular docking and additional MD simulations to propose possible complexes and evaluate their stability, focusing on high shape complementarity and involvement of beta 3 and beta 5 strands at the interfaces.
Article
Anesthesiology
Liang Han, Jie Jiang, Mengwen Xue, Tao Qin, Ying Xiao, Erxi Wu, Xin Shen, Qingyong Ma, Jiguang Ma
REGIONAL ANESTHESIA AND PAIN MEDICINE
(2020)
Article
Multidisciplinary Sciences
Xue-Jing Wang, Ming-Ming Ma, Le-Bo Zhou, Xiao-Yi Jiang, Miao-Miao Hao, Robert K. F. Teng, Erxi Wu, Bei-Sha Tang, Jia-Yi Li, Jun-Fang Teng, Xue-Bing Ding
NATURE COMMUNICATIONS
(2020)
Article
Neurosciences
Mingming Ma, Jing Yao, Yongkang Chen, Han Liu, Danhao Xia, Haiyan Tian, Xinxin Wang, Erxi Wu, Xuejing Wang, Xuebing Ding
FRONTIERS IN NEUROSCIENCE
(2020)
Article
Biochemistry & Molecular Biology
Xue-Bing Ding, Xin-Xin Wang, Dan-Hao Xia, Han Liu, Hai-Yan Tian, Yu Fu, Yong-Kang Chen, Chi Qin, Jiu-Qi Wang, Zhi Xiang, Zhong-Xian Zhang, Qin-Chen Cao, Wei Wang, Jia-Yi Li, Erxi Wu, Bei-Sha Tang, Ming-Ming Ma, Jun-Fang Teng, Xue-Jing Wang
Summary: Animal studies have suggested a link between meningeal lymphatic dysfunction and neurodegenerative diseases like Alzheimer's disease and Parkinson's disease. This study found that patients with idiopathic Parkinson's disease had reduced meningeal lymphatic flow and delayed cervical lymph node perfusion compared to patients with atypical Parkinsonian disorders. In mouse models, impaired meningeal lymphatic drainage was associated with worsened alpha-syn pathology and PD progression.
Article
Immunology
Qinqin Pu, Ping Lin, Pan Gao, Zhihan Wang, Kai Guo, Shugang Qin, Chuanmin Zhou, Biao Wang, Erxi Wu, Nadeem Khan, Zhenwei Xia, Xiawei Wei, Min Wu
Summary: The gut microbiota plays a vital role in regulating the migration of ILC2 cells through the gut-lung axis, influencing host defense against infection. The study shows that two types of ILC2 cells have distinct but crucial roles in host immunity.
JOURNAL OF IMMUNOLOGY
(2021)
Article
Immunology
Xinxin Wang, Haiyan Tian, Han Liu, Dongxiao Liang, Chi Qin, Qingyong Zhu, Lin Meng, Yu Fu, Shuqin Xu, Yanping Zhai, Xuebing Ding, Xuejing Wang
Summary: The study identified slowed flow through meningeal lymphatic vessels (mLVs) in patients with acute neuromyelitis optica spectrum disorders (NMOSD) compared to those in chronic phase, with the flow speed correlating with disease severity evaluated by expanded disability status scale (EDSS). Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) may offer objective evidence to predict NMOSD acute relapse by evaluating mLVs function. Promoting or restoring the function of mLVs may present a new target for NMOSD relapse treatment.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Chemistry, Medicinal
Dan Qi, Yunyi Liu, Juan Li, Jason H. Huang, Xiaoxiao Hu, Erxi Wu
Summary: Cancer stem cells (CSCs) are a small subpopulation of cells within a tumor that play a crucial role in various aspects of cancer development, making them attractive targets for cancer treatment. Salinomycin, identified as a potent anti-CSC agent in 2009, has broad-spectrum activities and potential for clinical application based on current understandings. Further research is needed to explore its mechanisms of action and translational potential.
MEDICINAL RESEARCH REVIEWS
(2022)
Article
Multidisciplinary Sciences
Xin Chen, Liang Sheng, Jiguang Ma, Dan Qi, Xuqi Li, Zheng Wang, Zheng Wu, Lucas Wong, Jason H. Huang, Erx Wu, Qingyon Ma, Dong Zhang
Summary: Cigarette smokers have a higher risk of pancreatic cancer, but the mechanisms of cigarette metabolites are not fully understood. This study demonstrates that NNK, a component of cigarette smoke, promotes the growth and migration of pancreatic cancer cells and the progression of chronic pancreatitis to pancreatic cancer. These findings provide potential strategies and targets for early prevention and treatment of pancreatic cancer.
Article
Engineering, Biomedical
Yunyi Liu, Cheng Peng, Hui Zhang, Juan Li, Hailong Ou, Yang Sun, Chaoqi Wen, Dan Qi, Xiaoxiao Hu, Erxi Wu, Weihong Tan
Summary: This study demonstrates that DNA aptamer S11e can accurately recognize fibrosarcoma cells and localize in the mitochondria, promoting cell apoptosis and inhibiting cell migration. Additionally, the study reveals the interaction between S11e and Diablo/SMAC protein, leading to the inhibition of fibrosarcoma cell migration and invasion.
BIOACTIVE MATERIALS
(2022)
Article
Multidisciplinary Sciences
Jing Lu, Ying Zhang, Dan Qi, Chunyan Yan, Benhao Wu, Jason H. Huang, Jianwen Yao, Erxi Wu, Guoying Zhang
Summary: Recent research has discovered that L-theanine from tea and its derivative TBrC have potential inhibitory activities against SARS-CoV-2, as well as anti-tumor effects on lung cancer cells without affecting normal lung cells. This suggests a potential protective effect of TBrC and L-theanine against pulmonary damage in patients infected with SARS-CoV-2, particularly lung cancer patients.
Review
Clinical Neurology
Dan Qi, Jing Li, C. Chad Quarles, Ekokobe Fonkem, Erxi Wu
Summary: This article summarizes the current challenges in the assessment of therapy response in patients with glioblastoma. It discusses the use of quantitative imaging, liquid biomarkers, and machine intelligence for the early prediction of therapy response and tumor progression to guide clinical decision making.
Article
Genetics & Heredity
Dan Qi, Yiqun Geng, Jacob Cardenas, Jinghua Gu, S. Stephen Yi, Jason H. H. Huang, Ekokobe Fonkem, Erxi Wu
Summary: Peripheral blood is being explored as a noninvasive alternative to tissue biopsy for developing biomarkers for glioblastoma (GBM), but the lack of a robust detection approach has hindered the identification of widely utilized blood-based biomarkers in clinical settings. This study introduces WBGR, a globin reduction technique for RNA sequencing of whole blood, and demonstrates its ability to detect GBM-associated transcriptomic changes. Through transcriptomic analysis of tumor tissues, a 10-gene panel (GBM-Dx panel) consisting of mRNA, long noncoding RNA, and microRNA was identified as a potential tool for early detection and clinical management of GBM. The integrated approach of WBGR offers comprehensive analytic capacity for blood-based marker identification.
NPJ GENOMIC MEDICINE
(2023)
Article
Biochemical Research Methods
Xingxin Pan, Zeynep H. Coban Akdemir, Ruixuan Gao, Xiaoqian Jiang, Gloria M. Sheynkman, Erxi Wu, Jason H. Huang, Nidhi Sahni, S. Stephen Yi
Summary: Alzheimer's disease (AD) is a complex neurodegenerative disease with genetic factors playing a key role in its occurrence. Previous studies on AD-associated genes have been limited by sample size and selection bias, calling for comprehensive research. To address this, we constructed a large-scale AD mutation framework and proposed deep learning models to effectively predict cognitive impairment based on genetic mutation profiles. Our study identified novel co-mutations that contribute to dementia, laying a foundation for targeted therapy and precision medicine.
BRIEFINGS IN BIOINFORMATICS
(2023)
Article
Biochemistry & Molecular Biology
Xingxin Pan, Jun Yun, Zeynep H. Coban Akdemir, Xiaoqian Jiang, Erxi Wu, Jason H. Huang, Nidhi Sahni, S. Stephen Yi
Summary: Discovering effective therapies for neurological and developmental disorders is difficult due to their complex and interactive mechanisms. Existing drugs for Alzheimer's disease are limited, especially for impacting cell death causes. This study developed a deep learning-based prediction framework to identify potential repurposed drug therapies for AD, which can also be applied to other diseases. The framework includes building a drug-target pair network, incorporating various features, and developing an AI-based DrugNet with robust predictive performance.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Rui Zhang, Yongkang Chen, Xinxin Wang, Haiyan Tian, Han Liu, Zhi Xiang, Dan Qi, Jason H. Huang, Erxi Wu, Xuebing Ding, Xuejing Wang
Summary: ALS is a progressive neurodegenerative disease characterized by pTDP-43-positive inclusions in neurons and glial cells. Injecting TDP-43 PFFs into Atg5(+/-) mice induced elevated levels of pTDP-43 and motor neuron dysfunction, providing evidence that autophagy deficiency promotes the formation and spreading of pathological TDP-43.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2021)