Review
Cell Biology
Gilberto Gonzalez, Lizhen Chen
Summary: This review summarizes the inhibitory role of EFA6 on axon regeneration through regulating microtubule dynamics and affecting ARF6 (ADP-ribosylation factor 6) GTPase-mediated integrin transport, highlighting its potential as a promising therapeutic strategy to promote axon regeneration and functional recovery after axon injury.
Article
Neurosciences
Menghon Cheah, Yuyan Cheng, Veselina Petrova, Anda Cimpean, Pavla Jendelova, Vivek Swarup, Clifford J. Woolf, Daniel H. Geschwind, James W. Fawcett
Summary: Sensory dorsal root ganglion (DRG) neurons in the peripheral branch regenerate readily after injury, but not in the central branch. However, expression of a9 integrin and its activator kindlin-1 (a9k1) enables axons to interact with tenascin-C, promoting extensive regeneration and reconnection of sensory axons in the spinal cord. Transcriptomic analyses of adult male rat DRG neurons revealed that a9k1 expression upregulates a known peripheral nerve regeneration program. Coupling a9k1 treatment with dorsal root axotomy leads to extensive central axonal regeneration, accompanied by the expression of a distinctive CNS regeneration program involving genes associated with ubiquitination, autophagy, ER, trafficking, and signaling. Pharmacological inhibition of these processes blocks axon regeneration, validating their causal contributions to sensory regeneration.
JOURNAL OF NEUROSCIENCE
(2023)
Article
Neurosciences
Yoshiki Sakai, Mayuka Tsunekawa, Kohei Ohta, Tatsuhiro Shimizu, Strahil Iv. Pastuhov, Hiroshi Hanafusa, Naoki Hisamoto, Kunihiro Matsumoto
Summary: In Caenorhabditis elegans hermaphrodites, axon injury activates TLN-1/talin through the cAMP-Epac-Rap GTPase cascade, leading to integrin inside-out activation and subsequent activation of the RhoA-ROCK signaling pathway. The C. elegans integrin signaling network regulates axon regeneration through the Src-RhoGEF-RhoA axis.
JOURNAL OF NEUROSCIENCE
(2021)
Review
Immunology
Shihan Xu, Tingwei Zhang, Zhengguo Cao, Wenjie Zhong, Chuangwei Zhang, Han Li, Jinlin Song
Summary: Integrin-alpha 9 beta 1 is a crucial cell membrane receptor with complex signaling pathways. It plays important roles in regulating cell physiological states and is involved in various diseases such as cancer, autoimmune diseases, nerve injury, and thrombosis.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Neurosciences
Yuichi Sekine, Ramakrishnan Kannan, Xingxing Wang, Stephen M. Strittmatter
Summary: Neural repair after traumatic spinal cord injury relies on axonal sprouting and regeneration. Rab GTPases were found to inhibit successful sprouting and regeneration. This study identified Rabphilin3A as an effector within regenerating axons, and its loss enhanced axon extension by increasing integrin action in the growth cone.
EXPERIMENTAL NEUROLOGY
(2022)
Article
Neurosciences
Hae Young Shin, Min Jung Kwon, Eun Mi Lee, Kyung Kim, Young Joo Oh, Hyung Soon Kim, Dong Hoon Hwang, Byung Gon Kim
Summary: The Myc proto-oncogene acts as a transcriptional hub gene in regulating the expression of a distinct subset of regeneration-associated genes (RAGs) in DRGs following preconditioning nerve injury. Deletion of Myc leads to a decrease in injury-induced expression of a specific subset of RAGs, which overlaps with the list of RAGs upregulated by Myc overexpression. Myc overexpression in DRGs post-spinal cord injury prevents sensory axon retraction through downstream RAG June, highlighting the critical role of Myc in axon regeneration.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Neurosciences
Kadidia Pemba Adula, Matthew Shorey, Vasudha Chauhan, Khaled Nassman, Shu-Fan Chen, Melissa M. Rolls, Alvaro Sagasti
Summary: DLK and LZK play different roles in zebrafish, promoting axon regeneration in motor neurons while inhibiting excessive growth in sensory neurons.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Multidisciplinary Sciences
Antonio Cadiz Diaz, Natalie A. Schmidt, Mamiko Yamazaki, Chia-Jung Hsieh, Thomas S. Lisse, Sandra Rieger
Summary: Tissue wounding induces axon regeneration through distinct mechanisms involving both neurons and keratinocytes, mediated by H2O2 signaling and matrix remodeling. These processes are essential for the regeneration of cutaneous axons after injury.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Editorial Material
Neurosciences
Nicole Y. Tsai, Derek S. Welsbie, Xin Duan
Summary: In this issue, three studies present new strategies for uncovering mediators of retinal neuroprotection and optic nerve regeneration, including transcriptional regulators and molecular targets.
Article
Biochemistry & Molecular Biology
Arthur W. English, Ken Berglund, Dario Carrasco, Katharina Goebel, Robert E. Gross, Robin Isaacson, Olivia C. Mistretta, Carly Wynans
Summary: Functional recovery after peripheral nerve injury is challenging due to slow and incomplete axon regeneration. Bioluminescent optogenetics, utilizing fusion proteins of luciferase and light-sensing ion channels, shows promise in enhancing axon regeneration by increasing neuronal excitability. Experimental studies in transgenic mice and viral vector-transduced mice demonstrate enhanced motor axon regeneration and successful muscle reinnervation after treatment with bioluminescent optogenetics.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Cell Biology
Mary L. Tapia, Gabriel Nascimento-dos-Santos, Kevin K. Park
Summary: This review discusses the heterogeneity of retinal ganglion cells (RGCs) and their differential resilience to injury and regeneration. By identifying molecular features and studying different regeneration models, specific RGC types that exhibit preferential survival and regeneration have been discovered. Cellular characteristics and the selective expression of certain genes may contribute to their reparative capacity. These studies lay an important groundwork for identifying factors that promote neural regeneration and developing targeted therapy for RGC degeneration and neurodegenerative diseases in general.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Clinical Neurology
Lei Yan, Zhiming Cui
Summary: This paper elucidates the important role of integrin beta 1 in different cells and its significance in the nervous system after injury. Microglia-expressed integrin beta 1 is mainly involved in promoting inflammatory damage, astrocyte-expressed integrin beta 1 plays a major role in axon regeneration, and endothelial cell-expressed integrin beta 1 participates in vascular remodeling. The location-dependent function of integrin beta 1 and its involvement in the inflammatory response of immune regulatory cells and axonal regeneration of neuronal cells are key to exploring repair after nervous system injury. The development of drugs targeting integrin beta 1 is expected to bring a breakthrough in the treatment of nervous system injury.
EUROPEAN NEUROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Ankita Kumari, Xin-An Zeng, Abdul Rahaman, Muhammad Adil Farooq, Yanyan Huang, Mahafooj Alee, Runyu Yao, Murtaza Ali, Ibrahim Khalifa, Omnia Badr
Summary: This study developed a simple and efficient in vivo assay using transgenic zebrafish larvae to identify compounds that can modulate M-cell regeneration. Through screening and in silico analysis, FDA-approved drugs with the potential to inhibit axon regeneration were identified, and PTEN and SOCS3 were identified as potential signaling molecules responsible for reducing axon regeneration. Additionally, the study demonstrated the toxic effects of these compounds.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Biology
Victoria L. Czech, Lauren C. O'Connor, Brendan Philippon, Emily Norman, Alexandra B. Byrne
Summary: TIR-1/dSarm/SARM1, a key regulator of axon degeneration, inhibits axon regeneration while promoting axon degeneration by interacting with different MAP kinase pathways. This mechanism is conserved in human SARM1. These findings provide critical insight into the multidimensional regulation of axon injury response and may inform strategies for repair.
Review
Chemistry, Multidisciplinary
Chuankai Dai, Xiaoming Liu, Rongyu Tang, Jiping He, Tatsuo Arai
Summary: In recent years, microfluidics has been crucial to the advancement of nerve regeneration research. Microfluidic devices accurately simulate the in vivo microenvironment for various research purposes such as analyzing growth inhibitory factors, screening drugs, evaluating nerve growth factors, and investigating neural injury and regeneration mechanisms. The platform enables precise control of cell behavior, such as neuron isolation, single-cell manipulation, neural patterning, and axon guidance, providing technical support for nerve regeneration.
APPLIED SCIENCES-BASEL
(2022)
Article
Neurosciences
Elena Maria Boggio, Erich M. Ehlert, Leonardo Lupori, Elizabeth B. Moloney, Fred De Winter, Craig W. Vander Kooi, Laura Baroncelli, Vasilis Mecollari, Bas Blits, James W. Fawcett, Joost Verhaagen, Tommaso Pizzorusso
MOLECULAR NEUROBIOLOGY
(2019)
Review
Biochemistry & Molecular Biology
James W. Fawcett
NEUROCHEMICAL RESEARCH
(2020)
Article
Neurosciences
K. Neumannova, L. Machova-Urdzikova, J. C. F. Kwok, J. W. Fawcett, P. Jendelova
EXPERIMENTAL NEUROLOGY
(2020)
Article
Multidisciplinary Sciences
Priscilla Day, Nuno Alves, Esther Daniell, Debayan Dasgupta, Rosalie Ogborne, Ashley Steeper, Mansoor Raza, Clare Ellis, James Fawcett, Roger Keynes, Elizabeth Muir
Article
Medicine, Research & Experimental
Bart Nieuwenhuis, Amanda C. Barber, Rachel S. Evans, Craig S. Pearson, Joachim Fuchs, Amy R. MacQueen, Susan van Erp, Barbara Haenzi, Lianne A. Hulshof, Andrew Osborne, Raquel Conceicao, Tasneem Z. Khatib, Sarita S. Deshpande, Joshua Cave, Charles Ffrench-Constant, Patrice D. Smith, Klaus Okkenhaug, Britta J. Eickholt, Keith R. Martin, James W. Fawcett, Richard Eva
EMBO MOLECULAR MEDICINE
(2020)
Article
Biochemistry & Molecular Biology
Bart Nieuwenhuis, Barbara Haenzi, Sam Hilton, Alejandro Carnicer-Lombarte, Barbara Hobo, Joost Verhaagen, James W. Fawcett
Summary: Adeno-associated viral vectors are commonly used for gene transfer in the nervous system, with promoter and viral vector serotype being key factors in determining transgene expression dynamics. This study compares the effectiveness of four promoters and finds that the mPGK and hSYN promoters result in the strongest transgene expression, with hSYN showing neuron-specific expression including in corticospinal neurons.
Editorial Material
Neurosciences
Frank Bradke, Simone Di Giovanni, James Fawcett
TRENDS IN NEUROSCIENCES
(2020)
Article
Multidisciplinary Sciences
Philippa M. Warren, Melissa R. Andrews, Marc Smith, Katalin Bartus, Elizabeth J. Bradbury, Joost Verhaagen, James W. Fawcett, Jessica C. F. Kwok
SCIENTIFIC REPORTS
(2020)
Article
Neurosciences
Susan van Erp, Annemiek A. van Berkel, Eline M. Feenstra, Pabitra K. Sahoo, Laura J. Wagstaff, Jeffery L. Twiss, James W. Fawcett, Richard Eva, Charles ffrench-Constant
Summary: The study demonstrates that efficient axon regeneration in younger axons is associated with local axonal protein synthesis, while reduced regeneration in mature axons is correlated with decreased levels of axonal proteins involved in translation. Furthermore, enhanced regeneration induced by co-culture with glial precursor cells is linked to increased axonal synthesis of proteins, including those constituting the translation machinery itself.
EXPERIMENTAL NEUROLOGY
(2021)
Article
Biochemistry & Molecular Biology
Serhiy Forostyak, Oksana Forostyak, Jessica C. F. Kwok, Nataliya Romanyuk, Monika Rehorova, Jan Kriska, Govindan Dayanithi, Ruma Raha-Chowdhury, Pavla Jendelova, Miroslava Anderova, James W. Fawcett, Eva Sykova
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Review
Biochemistry & Molecular Biology
Veselina Petrova, Bart Nieuwenhuis, James W. Fawcett, Richard Eva
Summary: The research focuses on utilizing various axonal organelles to promote regeneration in the injured adult CNS, highlighting their importance in developmental axon growth and discussing how they can be targeted.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Multidisciplinary
Philippa M. Warren, James W. Fawcett, Jessica C. F. Kwok
Summary: Chondroitin sulfate proteoglycans inhibit regeneration, neuroprotection, and plasticity following spinal cord injury. A second-generation chondroitinase ABC enzyme, mChABC, has shown reliable secretion and enhanced thermostability compared to the original bacterial chondroitinase (bChABC). The genetically modified enzyme effectively breaks down inhibitory extracellular matrix and promotes cellular integration and axonal growth, demonstrating promising potential for clinical application in treating spinal cord injuries.
Article
Biochemistry & Molecular Biology
Sujeong Yang, Sylvain Gigout, Angelo Molinaro, Yuko Naito-Matsui, Sam Hilton, Simona Foscarin, Bart Nieuwenhuis, Chin Lik Tan, Joost Verhaagen, Tommaso Pizzorusso, Lisa M. Saksida, Timothy M. Bussey, Hiroshi Kitagawa, Jessica C. F. Kwok, James W. Fawcett
Summary: Perineuronal nets (PNNs), containing chondroitin sulphate proteoglycans on neuronal surfaces, play a role in neuroplasticity and memory. Age-related reduction of chondroitin 6-sulphates (C6S) in PNNs leads to increased inhibition. Manipulating CS composition of PNNs can restore neuroplasticity and memory deficits in aged mice, with a focus on the importance of C6S in memory and neuroplasticity.
MOLECULAR PSYCHIATRY
(2021)
Article
Rehabilitation
Vieri Failli, Naomi Kleitman, Daniel P. Lammertse, Jane T. C. Hsieh, John D. Steeves, James W. Fawcett, Mark H. Tuszynski, Armin Curt, Michael G. Fehlings, James D. Guest, Andrew R. Blight
TOPICS IN SPINAL CORD INJURY REHABILITATION
(2021)
Article
Multidisciplinary Sciences
Veselina Petrova, Craig S. Pearson, Jared Ching, James R. Tribble, Andrea G. Solano, Yunfei Yang, Fiona M. Love, Robert J. Watt, Andrew Osborne, Evan Reid, Pete A. Williams, Keith R. Martin, Herbert M. Geller, Richard Eva, James W. Fawcett
NATURE COMMUNICATIONS
(2020)