Article
Cell Biology
Hye Ran Kim, Hye Jin Lee, Yewon Jeon, So Young Jang, Yoon Kyoung Shin, Jean Ho Yun, Hye Ji Park, Hyongjong Koh, Kyung Eun Lee, Jung Eun Shin, Hwan Tae Park
Summary: Autophagy is critical for clearing misfolded proteins and dysfunctional organelles in neurons. Autophagic stress in the peripheral nervous system is associated with neuropathy. The molecular mechanism of axonal degeneration due to autophagic stress in peripheral neurons is still unknown.
Article
Biochemistry & Molecular Biology
Pengfei Yuan, Fuhu Song, Pian Zhu, Keke Fan, Qinming Liao, Lijin Huang, Zhongjie Liu
Summary: This study reveals the regulatory role of PARP1 in the progression of painful diabetic neuropathy (PDN) through impairment of mitophagy. Inhibition of PARP1 and restoration of mitophagy function are potential therapeutic targets for PDN.
JOURNAL OF NEUROCHEMISTRY
(2022)
Article
Cell Biology
Clara Mutschler, Shaline V. Fazal, Nathalie Schumacher, Andrea Loreto, Michael P. Coleman, Peter Arthur-Farraj
Summary: Coculturing dissociated mouse Schwann cells (SCs) and dorsal root ganglion (DRG) neurons in microfluidic chambers can induce robust myelination and is a valuable technique for studying peripheral nervous system (PNS) myelination, injury, and regeneration. This model allows separate genetic manipulation of mouse SCs or neurons and can be used to complement in vivo mouse experiments. Live imaging of cocultures reveals that SCs are axo-protective and can clear axonal debris after traumatic axotomy.
JOURNAL OF CELL SCIENCE
(2023)
Article
Clinical Neurology
Ana Nascimento, Tiago F. Da Silva, Elisabete C. Fernandes, Liliana L. Luz, Fernando M. Mar, Boris Safronov, Monica M. Sousa
Summary: This study reveals the presence of axon initial segments (AIS) in sensory dorsal root ganglion (DRG) neurons and their role in spontaneous discharges in neuropathic pain. The AIS in myelinated DRG neurons contains sodium channels that are associated with spontaneous activity. Computer simulations suggest that the AIS plays a crucial role in initiating spontaneous discharges. The disruption of the AIS leads to mechanical allodynia in neuropathic pain, indicating its significance in chronic pain management.
Article
Neurosciences
Hong-Jun Cao, Li Huang, Meng-Ru Zheng, Tao Zhang, Ling-Chi Xu
Summary: This study comprehensively investigates the expression of circular RNAs in rat DRGs following injuries to the central and peripheral axon branches and identifies a total of 33 differentially expressed circular RNAs after central branch injury and 55 differentially expressed circular RNAs after peripheral branch injury. The functional enrichment analysis of host genes of differentially expressed circular RNAs reveals the involvement of the Hippo signaling pathway and Notch signaling pathway after both central and peripheral axon injuries.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Endocrinology & Metabolism
Mona Dastgheib, Seyed Vahid Shetab-Boushehri, Maryam Baeeri, Mahdi Gholami, Mohammad Yahya Karimi, Asieh Hosseini
Summary: The aim of this study was to evaluate the effects of rolipram and pentoxifylline on diabetic neuropathy (DN) and to determine the possible mechanisms involved in their effectiveness. The study found that the treatment with rolipram and/or pentoxifylline significantly improved motor function and reduced oxidative stress and inflammation in diabetic rats. The combination of rolipram and pentoxifylline showed the greatest effectiveness. These findings provide experimental evidence for further clinical investigations on the combination of these drugs for the treatment of DN.
METABOLIC BRAIN DISEASE
(2022)
Article
Cell Biology
Bo Pang, Ling Qiao, Shaoxin Wang, Xin Guo, Yun Xie, Liping Han
Summary: MiR-214-3p alleviated diabetes-induced nerve injury, pathological lesions, cell apoptosis, and inflammation in DRG through regulating Nav1.3 and TLR4 in STZ-induced rats. These findings suggest novel therapeutic targets for clinical treatment of diabetic neuropathy.
CELL BIOLOGY INTERNATIONAL
(2021)
Article
Biochemistry & Molecular Biology
Mohammadali Almasieh, Hannah Faris, Leonard A. Levin
Summary: Membrane phospholipids are essential for signaling pathways and their trafficking can be influenced by various events. The trafficking of phospholipids in the axonal membrane may play a role in axonal degeneration, regeneration and other processes.
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
(2022)
Article
Neurosciences
Farhana Naznin, T. M. Zaved Waise, Paul Fernyhough
Summary: Impairments in mitochondrial physiology, specifically the muscarinic acetylcholine type 1 receptor (M1R) pathway, play a role in the progression of neurodegenerative conditions such as peripheral neuropathy in diabetes. Inhibition of M1R using specific antagonists can prevent mitochondrial dysfunction and nerve degeneration. Activation of AMPK through pirenzepine and muscarinic toxin 7 (MT7) can improve sensory abnormalities and nerve fiber loss. The negative regulation of the M1R-dependent pathway could be a potential therapeutic target for enhancing mitochondrial function and repairing nerve damage.
MOLECULAR NEUROBIOLOGY
(2022)
Article
Cell Biology
Bin Pan, Di Guo, Li Jing, Ke Li, Xin Li, Gen Li, Xiao Gao, Zhi-Wen Li, Wei Zhao, Hu Feng, Meng-Han Cao
Summary: This study reveals the role of lncRNA Pvt1 in the repair of peripheral nerve injury and highlights it as a potential treatment target. The findings show that Pvt1 increases c-Jun expression through sponging miRNA-214, enhancing the proliferation and migration of Schwann cells, and improving the regeneration of injured sciatic nerves and locomotor function in mice.
NEURAL REGENERATION RESEARCH
(2023)
Article
Neurosciences
Andres de Leon, Julien Gibon, Philip A. Barker
Summary: NGF and BDNF are important trophic factors for sensory neurons during development, but the signaling pathways leading to their death differ, with BDNF-dependent sensory neuron degeneration potentially involving BAX and ROS.
Article
Pharmacology & Pharmacy
Onur Avci, Ercan Ozdemir, Ahmet Sevki Taskiran, Zeynep Deniz Sahin Inan, Sinan Gursoy
Summary: The study found that metformin can alleviate the tolerance to morphine in diabetic rats and exhibit anti-apoptotic activity in DRG neurons.
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Alexander Assmann, Vera Schmidt, Caroline Lepke, Yukiharu Sugimura, Anna Kathrin Assmann, Mareike Barth, Artur Lichtenberg, Payam Akhyari
Summary: This study provides evidence that oxidative stress plays a role in the degeneration of biological cardiovascular grafts. Rats deficient in superoxide dismutase 3 showed decreased antioxidant activity and exhibited regurgitation, intima hyperplasia, and calcification in the implanted grafts.
Article
Engineering, Biomedical
Mariya M. Mikhailova, Konstantin Sydoruk, Lubov Davydova, Evgeniy Yastremsky, Sergey N. Chvalun, Vladimir G. Debabov, Vladimir G. Bogush, Andrey A. Panteleyev
Summary: The study assessed the suitability of electrospun recombinant spidroin-based matrices for cultivation of the mouse aorta and dorsal root ganglia (DRG) explants, and quantified the effects of matrix topography on both types of tissues. The results showed that the RS-based matrices effectively supported aortic explants survival and sprouting, and matrices with parallel fibers highly oriented cell migration. The findings demonstrate that electrospun RS matrices are highly suitable for culturing both nerve and vascular cells, and studying the effects of matrix topography on cell migration.
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
(2022)
Article
Multidisciplinary Sciences
Rui Feng, Vishnu Muraleedharan Saraswathy, Mayssa H. Mokalled, Valeria Cavalli
Summary: Sensory neurons in the dorsal root ganglia (DRG) relay sensory information and undergo regenerative processes with the help of glial and immune cells. Macrophages in the DRG play a crucial role in promoting axon regeneration, and they possess self-renewal capacity. Through single-cell transcriptomics and communication simulation, it was found that DRGMacs express neuroprotective and glioprotective ligands and communicate with satellite glial cells. This heterogeneity and function of DRGMacs have potential implications for nerve injury treatment.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
Weiwei Cheng, Shaopeng Wang, Alexander A. Mestre, Chenglai Fu, Andres Makarem, Fengfan Xian, Lindsey R. Hayes, Rodrigo Lopez-Gonzalez, Kevin Drenner, Jie Jiang, Don W. Cleveland, Shuying Sun
NATURE COMMUNICATIONS
(2018)
Article
Neurosciences
Lindsey R. Hayes, Seneshaw A. Asress, Yingjie Li, Alexander Galkin, Anna Stepanova, Hibiki Kawamata, Giovanni Manfredi, Jonathan D. Glass
EXPERIMENTAL NEUROLOGY
(2019)
Article
Neurosciences
Lien Nguyen, Fabio Montrasio, Amrutha Pattamatta, Solaleh Khoramian Tusi, Olgert Bardhi, Kevin D. Meyer, Lindsey Hayes, Katsuya Nakamura, Monica Banez-Coronel, Alyssa Coyne, Shu Guo, Lauren A. Laboissonniere, Yuanzheng Gu, Saravanakumar Narayanan, Benjamin Smith, Roger M. Nitsch, Mark W. Kankel, Mia Rushe, Jeffrey Rothstein, Tao Zu, Jan Grimm, Laura P. W. Ranum
Article
Neurosciences
Weiwei Cheng, Shaopeng Wang, Zhe Zhang, David W. Morgens, Lindsey R. Hayes, Soojin Lee, Bede Portz, Yongzhi Xie, Baotram Nguyen, Michael S. Haney, Shirui Yan, Daoyuan Dong, Alyssa N. Coyne, Junhua Yang, Fengfan Xian, Don W. Cleveland, Zhaozhu Qiu, Jeffrey D. Rothstein, James Shorter, Fen-Biao Gao, Michael C. Bassik, Shuying Sun
Article
Biology
Lindsey R. Hayes, Lauren Duan, Kelly Bowen, Petr Kalab, Jeffrey D. Rothstein
Article
Neurosciences
Alyssa N. Coyne, Benjamin L. Zaepfel, Lindsey Hayes, Boris Fitchman, Yuval Salzberg, En-Ching Luo, Kelly Bowen, Hannah Trost, Stefan Aigner, Frank Rigo, Gene W. Yeo, Amnon Harel, Clive N. Svendsen, Dhruv Sareen, Jeffrey D. Rothstein
Letter
Rheumatology
Jemima Albayda, Lindsey R. Hayes, Lisa Christopher-Stine
Article
Chemistry, Multidisciplinary
Honghe Liu, Yu-Ning Lu, Tapas Paul, Goran Periz, Michael T. Banco, Adrian R. Ferre-D'Amare, Jeffrey D. Rothstein, Lindsey R. Hayes, Sua Myong, Jiou Wang
Summary: DHX36 is a robust positive regulator of C9orf72 RAN translation, facilitating the process by resolving repeat RNA G-quadruplex structures. It may serve as a potential target for therapeutic intervention in ALS and FTD associated with C9orf72 expansions.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Cell Biology
Benjamin L. Zaepfel, Zhe Zhang, Kirstin Maulding, Alyssa N. Coyne, Weiwei Cheng, Lindsey R. Hayes, Thomas E. Lloyd, Shuying Sun, Jeffrey D. Rothstein
Summary: The study found that overexpression of UPF1 protein can mitigate neurotoxicity in C9orf72 ALS/FTD models by reducing the severity of known neurodegenerative phenotypes without affecting NMD function itself.
Article
Multidisciplinary Sciences
Shaopeng Wang, Malgorzata J. Latallo, Zhe Zhang, Bo Huang, Dmitriy G. Bobrovnikov, Daoyuan Dong, Nathan M. Livingston, Wilson Tjoeng, Lindsey R. Hayes, Jeffrey D. Rothstein, Lyle W. Ostrow, Bin Wu, Shuying Sun
Summary: This study investigates the nuclear export and translation process of circular repeat-containing C9ORF72 intronic RNA using single molecule imaging, revealing the potential role of these repetitive RNAs in causing ALS and FTD and highlighting the importance of RNA spatial localization in disease etiology.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Lindsey R. Hayes, Lauren Duan, Svetlana Vidensky, Petr Kalab
Summary: Disruption of nucleocytoplasmic transport is increasingly recognized as a factor in the pathogenesis of neurodegenerative diseases. Neuronal nuclear membranes appear to be uniquely vulnerable to loss of cytoplasmic support, requiring improved methods to enhance nuclear stability.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2021)
Article
Neurosciences
Emily G. Baxi, Terri Thompson, Jonathan Li, Julia A. Kaye, Ryan G. Lim, Jie Wu, Divya Ramamoorthy, Leandro Lima, Vineet Vaibhav, Andrea Matlock, Aaron Frank, Alyssa N. Coyne, Barry Landin, Loren Ornelas, Elizabeth Mosmiller, Sara Thrower, S. Michelle Farr, Lindsey Panther, Emilda Gomez, Erick Galvez, Daniel Perez, Imara Meepe, Susan Lei, Berhan Mandefro, Hannah Trost, Louis Pinedo, Maria G. Banuelos, Chunyan Liu, Ruby Moran, Veronica Garcia, Michael Workman, Richie Ho, Stacia Wyman, Jennifer Roggenbuck, Matthew B. Harms, Jennifer Stocksdale, Ricardo Miramontes, Keona Wang, Vidya Venkatraman, Ronald Holewenski, Niveda Sundararaman, Rakhi Pandey, Danica-Mae Manalo, Aneesh Donde, Nhan Huynh, Miriam Adam, Brook T. Wassie, Edward Vertudes, Naufa Amirani, Krishna Raja, Reuben Thomas, Lindsey Hayes, Alex Lenail, Aianna Cerezo, Sarah Luppino, Alanna Farrar, Lindsay Pothier, Carolyn Prina, Todd Morgan, Arish Jamil, Sarah Heintzman, Jennifer Jockel-Balsarotti, Elizabeth Karanja, Jesse Markway, Molly McCallum, Ben Joslin, Deniz Alibazoglu, Stephen Kolb, Senda Ajroud-Driss, Robert Baloh, Daragh Heitzman, Tim Miller, Jonathan D. Glass, Natasha Leanna Patel-Murray, Hong Yu, Ervin Sinani, Prasha Vigneswaran, Alexander V. Sherman, Omar Ahmad, Promit Roy, Jay C. Beavers, Steven Zeiler, John W. Krakauer, Carla Agurto, Guillermo Cecchi, Mary Bellard, Yogindra Raghav, Karen Sachs, Tobias Ehrenberger, Elizabeth Bruce, Merit E. Cudkowicz, Nicholas Maragakis, Raquel Norel, Jennifer E. Van Eyk, Steven Finkbeiner, James Berry, Dhruv Sareen, Leslie M. Thompson, Ernest Fraenkel, Clive N. Svendsen, Jeffrey D. Rothstein
Summary: Answer ALS is a resource that includes patient-derived iPS cell lines, multi-omic data from iPS neurons, and clinical and smartphone data from over 1,000 ALS patients. This data can be used to identify distinct disease subgroups in ALS.
NATURE NEUROSCIENCE
(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
Cell Biology
Lauren Duan, Benjamin L. Zaepfel, Vasilisa Aksenova, Mary Dasso, Jeffrey D. Rothstein, Petr Kalab, Lindsey R. Hayes
Summary: The nuclear clearance of TDP-43 is a characteristic of neurodegenerative diseases. This study reveals that the nuclear export of TDP-43 is facilitated by the binding of nuclear RNAs, and the balance of transcription, pre-mRNA processing, and RNA export regulates the nuclear localization of TDP-43.
Article
Neurosciences
Yini Li, Xiaoyang Dou, Jun Liu, Yu Xiao, Zhe Zhang, Lindsey Hayes, Rong Wu, Xiujuan Fu, Yingzhi Ye, Bing Yang, Lyle W. Ostrow, Chuan He, Shuying Sun
Summary: Global reduction of m(6)A leads to mRNA stabilization and repeat RNA decay in C9ORF72-ALS/FTD. Elevating m(6)A reduces repeat RNA and dipeptide repeats, restores mRNA homeostasis, and improves patient neuron survival.
NATURE NEUROSCIENCE
(2023)