Article
Cell Biology
Stacey Anne Gould, Jonathan Gilley, Karen Ling, Paymaan Jafar-Nejad, Frank Rigo, Michael Coleman
Summary: Activation of SARM1 protein leads to programmed axon degeneration, but lowering its levels can delay this process, as demonstrated in haploinsufficient mice. SARM1-lowering agents show therapeutic potential for neuroprotection.
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)
Review
Cell Biology
Satpal Virdee
Summary: This article summarizes the research developments regarding the unusual features of MYCBP2 and proposes therapeutic strategies to prevent neurodegenerative diseases.
NEURAL REGENERATION RESEARCH
(2022)
Review
Genetics & Heredity
Kai Zhang, Mingsheng Jiang, Yanshan Fang
Summary: Significant progress has been made in recent years in identifying the genetic components of Wallerian degeneration, shedding light on the active and dynamic cellular process at molecular and cellular levels. By highlighting the key players and outlining the molecular script of Wallerian degeneration, a useful framework has been provided to understand and develop new therapeutic strategies for axon degeneration in neural injury and neurodegenerative disease.
ANNUAL REVIEW OF GENETICS, VOL 55
(2021)
Article
Medicine, Research & Experimental
Caitlin B. Dingwall, Amy Strickland, Sabrina W. Yum, Aldrin K. Y. Yim, Jian Zhu, Peter L. Wang, Yurie Yamada, Robert E. Schmidt, Yo Sasaki, A. Joseph Bloom, Aaron DiAntonio, Jeffrey Milbrandt
Summary: This study identified rare NMNAT2 gene variants associated with a neuropathy syndrome and demonstrated the importance of SARM1-related neuroimmune mechanisms in disease pathogenesis. Macrophage depletion therapy was shown to block and reverse neuropathic phenotypes in mice with NMNAT2 mutations.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Neurosciences
Yi-Hsien Chen, Yo Sasaki, Aaron DiAntonio, Jeffrey Milbrandt
Summary: Research has shown that SARM1 triggers axon degeneration in human neurons, and SARM1 inhibitors are proposed as a potential new therapy for the prevention and treatment of neurological diseases.
EXPERIMENTAL NEUROLOGY
(2021)
Article
Critical Care Medicine
Athanasios S. S. Alexandris, Youngrim Lee, Mohamed Lehar, Zahra Alam, James McKenney, Dianela Perdomo, Jiwon Ryu, Derek Welsbie, Donald J. J. Zack, Vassilis E. E. Koliatsos
Summary: Traumatic axonal injury (TAI) is a common neuropathology in traumatic brain injury (TBI) and is caused by rotational acceleration of the head. TAI in the optic nerve is frequently observed in TBI models and provides a good model for studying TAI mechanisms and treatments. This study investigated the role of SARM1 in the breakdown of distal and proximal segments of the optic nerve following TBI and found that Sarm1 knockout had a significant effect in suppressing axonal degeneration in the distal optic nerve, with no effect on initial traumatic disconnection or proximal optic axonopathy.
JOURNAL OF NEUROTRAUMA
(2023)
Article
Clinical Neurology
Eduardo Benarroch
Summary: Axonal loss is a significant issue in neurologic disorders and efforts have been made to prevent it. Studies using Wld(s) mutant mouse model have provided important insights into the mechanisms of axon death. Mitochondria play a critical role in the initiation of axonal degeneration. The basic pathways for axon injury are relevant in a wide range of neurologic disorders, and identifying central regulators and biomarkers of this process may lead to potential therapeutic targets for axonal protection.
Article
Neurosciences
Shuai Wang, Mingxue Song, Hui Yong, Cuiqin Zhang, Kang Kang, Zhidan Liu, Yiyu Yang, Zhengcheng Huang, Shu'e Wang, Haotong Ge, Xiulan Zhao, Fuyong Song
Summary: This study reveals the importance of mitochondrial localization of SARM1 in programmed axon death. Mitochondrial accumulation of SARM1 interferes with mitochondrial dynamics and activates PINK1-mediated mitophagy, contributing to axonal degeneration. Rapamycin intervention eliminates mitochondrial accumulation of SARM1 and partially attenuates neuropathy. The findings suggest that mitochondrial localization of SARM1 plays a role in its clearance through the SARM1-PINK1 mitophagy pathway.
MOLECULAR NEUROBIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Janneke D. Icso, Paul R. Thompson
Summary: During axon degeneration, NAD+ levels are controlled by NMNAT2 and SARM1. NMNAT2 catalyzes the formation of NAD(+) from NMN and ATP, while SARM1 catalyzes the hydrolysis of NAD(+) to decrease its concentration. SARM1 knockout decreases axon degeneration and shows therapeutic potential.
CURRENT OPINION IN CHEMICAL BIOLOGY
(2022)
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
Biotechnology & Applied Microbiology
Fang Fang, Pei Zhuang, Xue Feng, Pingting Liu, Dong Liu, Haoliang Huang, Liang Li, Wei Chen, Liang Liu, Yang Sun, Haowen Jiang, Jiangbin Ye, Yang Hu
Summary: Our study identified the decreased expression of NMNAT2 in glaucomatous RGCs, leading to a decline in NAD(+) levels. Modulating the levels of NMNAT2 in RGCs using AAV2-mSncg vector can effectively restore NAD(+) levels and provide neuroprotection and preservation of visual function.
Article
Neurosciences
Shilpa Sambashivan, Marc R. Freeman
Summary: Axon degeneration is a major feature in the injured nervous system, driven by the protein SARM1 which actively promotes NAD(+) loss after injury. While SARM1 is believed to act as a sensor for metabolic changes and drive degeneration, its biology is complex and there is still much to learn about its role in governing nervous system responses to injury or disease.
CURRENT OPINION IN NEUROBIOLOGY
(2021)
Article
Cell Biology
Sean Mccracken, Michael J. Fitzpatrick, Allison L. Hall, Zelun Wang, Daniel Kerschensteiner, Josh L. Morgan, Philip R. Williams
Summary: Retinal ganglion cell (RGC) degeneration, caused by axon degeneration, is the main reason for vision loss in blinding conditions. Axonal Ca2+ elevations from optic nerve injury do not reach RGC somas, and baseline Ca2+ levels of RGCs predict their survival after axon injury.
Review
Clinical Neurology
Peter Arthur-Farraj, Michael P. Coleman
Summary: This review summarizes the latest advances in laboratory traumatic peripheral nerve injury studies, focusing on axon degeneration and repair Schwann cell formation at the molecular level. Studies have identified key genes and proteins playing important roles in nerve injury and disease development, providing insights into potential therapeutic approaches for peripheral nerve disorders.
Article
Multidisciplinary Sciences
Jonathan E. Farley, Thomas C. Burdett, Romina Barria, Lukas J. Neukomm, Kevin P. Kenna, John E. Landers, Marc R. Freeman
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2018)
Article
Neurosciences
Gaynor A. Smith, Tzu-Huai Lin, Amy E. Sheehan, Wynand Van der Goes van Naters, Lukas J. Neukomm, Hillary K. Graves, Dana M. Bis-Brewer, Stephan Zuchner, Marc R. Freeman
Article
Multidisciplinary Sciences
Maria Paglione, Arnau Llobet Rosell, Jean-Yves Chatton, Lukas J. Neukomm
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2020)
Article
Neurosciences
Leticia Perez-Sisques, Nuria Martin-Flores, Merce Masana, Julia Solana-Balaguer, Arnau Llobet, Joan Romani-Aumedes, Merce Canal, Genis Campoy-Campos, Esther Garcia-Garcia, Nuria Sanchez-Fernandez, Sara Fernandez-Garcia, James P. Gilbert, Manuel Jose Rodriguez, Heng-Ye Man, Elena Feinstein, David L. Williamson, David Soto, Xavier Gasull, Jordi Alberch, Cristina Malagelada
Summary: The study reveals the crucial role of RTP801 in neuronal plasticity and motor learning. Knockdown of RTP801 enhances excitatory synaptic transmission and improves motor learning, while also regulating spine density and synaptic-related protein levels.
EXPERIMENTAL NEUROLOGY
(2021)
Article
Genetics & Heredity
Kelsey A. A. Herrmann, Yizhou Liu, Arnau Llobet-Rosell, Colleen N. N. McLaughlin, Lukas J. J. Neukomm, Jaeda C. C. Coutinho-Budd, Heather T. T. Broihier
Summary: This study reveals divergent signaling requirements for dSARM in glial phagocytosis and axon degeneration. The results demonstrate that the NAD(+) hydrolase activity of dSARM is essential for both functions, while SAM domain-mediated multimerization is only important for axon degeneration. In addition, dSARM functions in a genetic pathway with MAP3K Ask1 during development.
Article
Neurosciences
Shih-Te Hung, Arnau Llobet Rosell, Daphne Jurriens, Marijn Siemons, Oleg Soloviev, Lukas C. C. Kapitein, Kristin Grussmayer, Lukas J. J. Neukomm, Michel Verhaegen, Carlas Smith
Summary: Single-molecule localization microscopy (SMLM) enables high-resolution visualization of organelle structures and individual protein localization. However, imaging conditions in tissue often lead to decreased resolution. In this study, the combination of sensorless adaptive optics, in-situ 3D point spread function (PSF) calibration, and a single-objective lens inclined light sheet microscope (AO-SOLEIL) mitigates tissue-induced deteriorations and improves imaging resolution and sub-cellular structure visualization.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Biology
Arnau Llobet Rosell, Maria Paglione, Jonathan Gilley, Magdalena Kocia, Giulia Perillo, Massimiliano Gasparrini, Lucia Cialabrini, Nadia Raffaelli, Carlo Angeletti, Giuseppe Orsomando, Pei-Hsuan Wu, Michael P. Coleman, Andrea Loreto, Lukas Jakob Neukomm
Summary: This study demonstrates the critical role of NMN in neurodegeneration in flies, beyond axonal injury, by successfully preserving severed axons through lowering NMN levels.
Article
Multidisciplinary Sciences
Aron Szabo, Virag Vincze, Aishwarya Sanjay Chhatre, Andras Jipa, Sarolta Bognar, Katalin Eszter Varga, Poulami Banik, Adel Harmatos-Urmosi, Lukas J. Neukomm, Gabor Juhasz
Summary: Glial engulfment of neuron-derived debris after trauma, during development, and in neurodegenerative diseases supports nervous system functions. However, mechanisms governing the efficiency of debris degradation in glia have remained largely unexplored. Our study shows that LC3-associated phagocytosis (LAP), an engulfment pathway assisted by certain autophagy factors, promotes glial phagosome maturation and the clearance of neuronal debris, contributing to the recovery of the injured nervous system.
NATURE COMMUNICATIONS
(2023)
Article
Developmental Biology
Clarisse Perron, Pascal Carme, Arnau Llobet Rosell, Eva Minnaert, Salome Ruiz-Demoulin, Heloise Szczkowski, Lukas Jakob Neukomm, Jean-Maurice Dura, Ana Boulanger
Summary: During animal development, neuronal circuits go through a period of refinement, which involves the removal of debris produced by neurons. Glial cells, particularly astrocytes, play a crucial role in phagocytosis and clearing this neuronal debris. Orion, a chemokine-like factor secreted by mushroom body neurons, is involved in the activation and transformation of astrocytes into phagocytes, as well as triggering glial infiltration, engulfment, and phagocytosis.