Article
Multidisciplinary Sciences
Brett A. McCray, Erika Diehl, Jeremy M. Sullivan, William H. Aisenberg, Nicholas W. Zaccor, Alexander R. Lau, Dominick J. Rich, Benedikt Goretzki, Ute A. Hellmich, Thomas E. Lloyd, Charlotte J. Sumner
Summary: TRPV4 interacts with RhoA, affecting cell structure. The neuropathy effects of TRPV4 are related to incorrect binding with RhoA. Inhibition of RhoA can restore neurite length.
NATURE COMMUNICATIONS
(2021)
Review
Neurosciences
Abhishek Roy, Zarna Pathak, Hemant Kumar
Summary: The difficulties in regenerating after CNS injuries, including spinal cord injury, are attributed to factors such as hypertrophic scarring, inhibitory molecules, and the absence of mechanisms responsible for axonal regeneration in the adult CNS. Strategies to improve axon regeneration include neutralizing inhibitors/proteins and stabilizing microtubules. Furthermore, the focus on counteracting inhibitors of axonal growth and their downstream signaling through the RhoA/ROCK pathway is emphasized.
EXPERIMENTAL NEUROLOGY
(2021)
Review
Biochemistry & Molecular Biology
Cong Li, Wu Xiong, Bowen Wan, Guang Kong, Siming Wang, Yingying Wang, Jin Fan
Summary: Secondary spinal cord injury is caused by an irreversible inflammatory response cascade, and the immune system plays a crucial role in mediating inflammation. Investigating the mechanisms and functions of peripheral immune cells at the site of injury is significant for identifying clinical therapeutic targets.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Ben Kaplan, Shulamit Levenberg
Summary: Peripheral nerve and spinal cord injuries have significant impacts on patients' lives, with severe cases currently lacking a cure. Biomaterials can be engineered as scaffolds to mimic nerve tissue and promote axonal regeneration, as well as deliver therapeutic agents to the site of injury.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Kirill D. Nadezhdin, Irina A. Talyzina, Aravind Parthasarathy, Arthur Neuberger, David X. Zhang, Alexander I. Sobolevsky
Summary: Nadezhdin et al. present structures of human TRPV4 in complex with the GTPase RhoA, revealing the mechanisms of channel activation, inhibition, and disease-causing mutations. TRPV4 is a polymodal cellular sensor involved in various physiological processes and diseases. The study demonstrates the interaction between TRPV4 and RhoA, identifies the binding sites of agonist 4α-PDD and inhibitor HC-067047, and provides insights into the activation and inhibition of TRPV4, laying the foundation for the development of therapeutics for TRPV4-related diseases.
NATURE COMMUNICATIONS
(2023)
Article
Neurosciences
Jesse K. Niehaus, Bonnie Taylor-Blake, Lipin Loo, Jeremy M. Simon, Mark J. Zylka
Summary: Peripheral nerve injury leads to long-term pro-inflammatory responses in spinal cord glial cells, but the identity of endogenous cells that resolve spinal inflammation has not been determined. Our study demonstrates that MRC1(+) spinal cord macrophages actively restrain glia to limit neuroinflammation and resolve mechanical pain following superficial injury, suggesting that therapeutic modulation of spinal macrophages could promote long-lasting recovery of neuropathic pain.
Article
Medicine, General & Internal
Jaclyn R. Wecht, William M. Savage, Grace O. Famodimu, Gregory A. Mendez, Jonah M. Levine, Matthew T. Maher, Joseph P. Weir, Jill M. Wecht, Jason B. Carmel, Yu-Kuang Wu, Noam Y. Harel
Summary: The study found that subthreshold TSCS can facilitate hand muscle responses to motor cortex stimulation, especially when the TSCS arrives simultaneously or slightly after the cortical stimulation, indicating the potential for enhanced synaptic plasticity in circuits serving hand function.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Neurosciences
Jacob Kjell, Mikael Svensson
Summary: Peripheral nerves have the ability to promote axon growth and regeneration, making them a potential repair strategy for spinal cord injuries. However, there is still limited understanding of the formation of new circuitries and functional outcomes associated with the use of peripheral nerve grafts.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Review
Immunology
Jiansong Chen, Yiguo Shen, Xiaobo Shao, Weiliang Wu
Summary: Spinal cord injury (SCI) and spinal cord tumor cause significant damage to the spinal cord, leading to multiple impairments and high morbidity and mortality. The treatment options for these conditions are limited and the underlying molecular mechanisms remain unclear. In the review, the role of inflammasomes in SCI and spinal cord tumors is highlighted, and targeting inflammasomes is suggested as a potential therapeutic strategy.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Neurosciences
Nathan T. Fiore, Zhuoran Yin, Dilansu Guneykaya, Christian D. Gauthier, Jessica Hayes, Aaron D'Hary, Oleg Butovsky, Gila Moalem-Taylor
Summary: Neuropathic pain is associated with the activation of glial cells, particularly microglia, in the central nervous system. This study found that microglia play a sexually dimorphic role in neuropathic pain in rodent models. Analysis of microglial gene expression revealed no common transcriptional changes in different neuropathic models, but a significant change was observed in the lumbar spinal cord after chronic constriction injury. Furthermore, male microglia from nerve-injured mice showed a unique transcriptional signature and increased phagocytotic activity. These findings suggest that spinal microglia contribute to sex-specific pain processing following nerve injury.
Article
Biochemistry & Molecular Biology
Tao Jiang, Tao Qin, Peng Gao, Zhiwen Tao, Xiaowei Wang, Mengyuan Wu, Jun Gu, Bo Chu, Ziyang Zheng, Jiang Yi, Tao Xu, Yifan Huang, Hao Liu, Shujie Zhao, Yongxin Ren, Jian Chen, Guoyong Yin
Summary: The expression of SIRT1 in spinal cord endothelial cells is decreased after spinal cord injury (SCI). SIRT1 has the ability to reduce endothelial reactive oxygen species production and protect endothelial barrier function, indicating its potential as a therapeutic target for promoting functional recovery against blood-spinal cord barrier (BSCB) disruption following SCI.
Article
Biochemistry & Molecular Biology
Baokun Zhang, Fangqi Lin, Jiqing Dong, Jingwen Liu, Zhenyu Ding, Jianguang Xu
Summary: This study demonstrates that PM-Exos can promote recovery in spinal cord injury patients by activating microglial autophagy and enhancing the polarization of anti-inflammatory type microglia, potentially through inhibition of the PI3K/AKT/mTOR signaling pathway.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2021)
Article
Anesthesiology
Courtney A. Bannerman, Katya Douchant, Julia P. Segal, Mitra Knezic, Alexandra E. Mack, Caitlin Lundell-Creagh, Jaqueline R. Silva, Scott Duggan, Prameet Sheth, Nader Ghasemlou
Summary: Chronic pain is a common complication of spinal cord injury. This study developed a mouse model of spinal cord injury and observed the pain phenotype and related pathology after injury. The study also investigated the changes in the gastrointestinal microbiome.
Article
Neurosciences
Xiaoping Ren, Weihua Zhang, Jie Qin, Jian Mo, Yi Chen, Jie Han, Xinjian Feng, Sitan Feng, Haibo Liang, Liangjue Cen, Xiaofei Wu, Linxuan Han, Rongyu Lan, Haixuan Deng, Huihui Yao, Zhongquan Qi, Hongjun Gao, Lishan Wei, Shuai Ren
Summary: This study tested spinal cord fusion (SCF) using the neuroprotective agent polyethylene glycol (PEG) in different animal models and developed a new clinical procedure called vascular pedicle hemisected spinal cord transplantation (vSCT) for the treatment of paraplegic patients. The results demonstrated the feasibility and efficacy of vSCT in re-establishing the continuity of spinal nerve fibers, potentially restoring motor, sensory, and autonomic nervous functions in paraplegic patients. Further clinical trials are needed to validate these findings.
CNS NEUROSCIENCE & THERAPEUTICS
(2022)
Article
Chemistry, Multidisciplinary
Taoyang Yuan, Yu Shao, Xu Zhou, Qian Liu, Zhichao Zhu, Bini Zhou, Yuanchen Dong, Nicholas Stephanopoulos, Songbai Gui, Hao Yan, Dongsheng Liu
Summary: Researchers have developed a DNA hydrogel to repair spinal cord gap in rats, promoting proliferation and differentiation of stem cells for functional recovery. This hydrogel system shows great potential in clinical trials and could be adaptable to other tissue regeneration applications.
ADVANCED MATERIALS
(2021)
Article
Biochemistry & Molecular Biology
Nikita K. Ussin, Anna M. Bagnell, Lesa R. Offermann, Rawan Abdulsalam, Makenzie L. Perdue, Patrick Magee, Maksymilian Chruszcz
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2018)
Article
Multidisciplinary Sciences
Tongguang Wang, Marie Medynets, Kory R. Johnson, Tara T. Doucet-O, Brianna DiSanza, Wenxue Li, Yadi Xu, Anna Bagnell, Richa Tyagi, Kevon Sampson, Nasir Malik, Joseph Steiner, Alina Hadegan, Jeffrey Kowalak, James O'Malley, Dragan Maric, Avindra Nath
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Biochemistry & Molecular Biology
William H. Aisenberg, Brett A. McCray, Jeremy M. Sullivan, Erika Diehl, Lauren R. DeVine, Jonathan Alevy, Anna M. Bagnell, Patrice Carr, Jack K. Donohue, Benedikt Goretzki, Robert N. Cole, Ute A. Hellmich, Charlotte J. Sumner
Summary: This study reveals that ubiquitination can regulate the activity of TRPV4 ion channel through multiple mechanisms, including ubiquitination of intracellular N-terminal and C-terminal intrinsically disordered regions. This ubiquitination can modulate TRPV4 channel function independently of its plasma membrane localization, and the ubiquitination of mutant TRPV4 is closely related to TRPV4 neuropathy.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Seonhye Cheon, Allison M. Culver, Anna M. Bagnell, Foster D. Ritchie, Janay M. Vacharasin, Mikayla M. McCord, Carin M. Papendorp, Evelyn Chukwurah, Austin J. Smith, Mara H. Cowen, Trevor A. Moreland, Pankaj S. Ghate, Shannon W. Davis, Judy S. Liu, Sofia B. Lizarraga
Summary: ASH1L plays a role in regulating neuronal morphogenesis by counteracting the catalytic activity of PRC2. Depletion of ASH1L leads to decreased neurite outgrowth and decreased expression of the gene TrkB, which is linked to neuronal morphogenesis. The neuronal morphogenesis defect can be overcome by inhibiting PRC2 activity.
MOLECULAR PSYCHIATRY
(2022)