Article
Chemistry, Medicinal
Kang Le, Michael J. J. Soth, Jason B. B. Cross, Gang Liu, William J. J. Ray, Jiacheng Ma, Sunil G. G. Goodwani, Paul J. J. Acton, Virginie Buggia-Prevot, Onno Akkermans, John Barker, Michael L. L. Conner, Yongying Jiang, Zhen Liu, Paul McEwan, Jennifer Warner-Schmidt, Alan Xu, Matthias Zebisch, Cobi J. J. Heijnen, Brett Abrahams, Philip Jones
Summary: Chemotherapy-induced peripheral neuropathy (CIPN) is a significant medical issue without sufficient treatment options. However, the discovery of DLK as a target presents a potential solution for treating neuronal injury and neurodegenerative diseases caused by CIPN. The development of potent DLK inhibitors, such as IACS-52825 (22), has shown promising results in reversing mechanical allodynia in mouse models of CIPN.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Lian Xu, Zhifeng Chen, Xiaodi Li, Hui Xu, Yu Zhang, Weiwei Yang, Jing Chen, Shuqiang Zhang, Lingchi Xu, Songlin Zhou, Guicai Li, Bin Yu, Xiaosong Gu, Jian Yang
Summary: This study re-analyzed 21 RNA-seq datasets and identified 53 evolutionarily conserved injury response genes, including species-preference injury response candidates and genes related to pre-regenerative and regenerating states. Furthermore, a large sex difference in response to sciatic nerve injury was found.
Article
Neurosciences
Junmi M. Saikia, Carmine L. Chavez-Martinez, Noah D. Kim, Sahar Allibhoy, Hugo J. Kim, Lidiya Simonyan, Samraa Smadi, Kristen M. Tsai, Daniel Romaus-Sanjurjo, Yishi Jin, Binhai Zheng
Summary: This study reveals the crucial role of dual leucine-zipper kinase (DLK) and leucine zipper kinase (LZK) in axonal repair after spinal cord injury. Deletion of both DLK and LZK inhibits axonal regeneration and sprouting induced by PTEN deletion, as well as naturally-occurring axon sprouting after injury. Interestingly, DLK and LZK play a role in both injured and uninjured neurons.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Jingwen Niu, Sabrina M. Holland, Andrea Ketschek, Kaitlin M. Collura, Natasha L. Hesketh, Takashi Hayashi, Gianluca Gallo, Gareth M. Thomas
Summary: This article investigates the relationship between dual leucine-zipper kinase (DLK) and the neural-specific isoform JNK3, and finds that JNK3 activates DLK by positive feedback phosphorylation and locks it in a highly active state. Unlike the JNK1 isoform, JNK2 and JNK3 promote prodegenerative signaling. Additionally, palmitoylation plays an important role in the axonal localization of DLK and JNK3, as well as in axonal retrograde signaling in response to optic nerve injury.
Article
Biochemistry & Molecular Biology
Suman Koirala, Rajarshi Roy, Sunanda Samanta, Subhasmita Mahapatra, Parimal Kar
Summary: Recent findings have emphasized the important role of dual leucine zipper kinase (DLK) in neuronal degeneration. Saraswatharishta (SWRT), a traditional Indian medicine, has shown effectiveness in treating neurodegenerative diseases. This study aims to explore the detailed mechanism of action of phytochemicals in SWRT against DLK. By screening over 500 phytochemicals derived from the main ingredients of SWRT, four novel compounds were identified and further investigated through molecular dynamics simulations. Among these compounds, CID16066851 from Acorus calamus showed the most stable interaction with DLK. The study identified key residues and highlighted the significance of electrostatic and van der Waals interactions in the binding process. The findings suggest potential for future drug development targeting neurodegenerative conditions.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biology
Yunbo Li, Erin M. Ritchie, Christopher L. Steinke, Cai Qi, Lizhen Chen, Binhai Zheng, Yishi Jin
Summary: The conserved MAP3Ks DLK and LZK play critical roles in Purkinje cells, with DLK activation leading to rapid death and LZK activation causing slow degeneration. Each kinase induces JNK activation and apoptosis through distinct pathways. Deletion of CELF2 significantly attenuates LZK-induced Purkinje cell degeneration. Controlling the activity levels of DLK and LZK is crucial for neuronal survival and health.
Article
Virology
Sara Dochnal, Husain Y. Merchant, Austin R. Schinlever, Aleksandra Babnis, Daniel P. Depledge, Angus C. Wilson, Anna R. Cliffe
Summary: Understanding the mechanisms of HSV-1 latent infection and reactivation in neurons is crucial for developing therapeutic strategies. In this study, a new in vitro model was established using a cell-to-cell spread-defective HSV-1 reporter virus. The study found that the reactivation process is biphasic and independent of secondary infection. These findings provide valuable insights into the molecular mechanisms of HSV-1 reactivation.
JOURNAL OF VIROLOGY
(2022)
Article
Biology
Michael J. Abrams, Fayth Hui Tan, Yutian Li, Ty Basinger, Martin L. Heithe, Anish Sarma, Iris T. Lee, Zevin J. Condiotte, Misha Raffiee, John O. Dabiri, David A. Gold, Lea Goentoro
Summary: The ability of animals to regenerate is a sliding scale, with some animals able to fully regenerate while others can only scar. Different animals may have varying abilities to activate the regeneration process, and supplementing their diet with additional nutrients could potentially switch on regeneration.
Article
Genetics & Heredity
Fei Liu, Yayun Qin, Yuwen Huang, Pan Gao, Jingzhen Li, Shanshan Yu, Danna Jia, Xiang Chen, Yuexia Lv, Jiayi Tu, Kui Sun, Yunqiao Han, James Reilly, Xinhua Shu, Qunwei Lu, Zhaohui Tang, Chengqi Xu, Daji Luo, Mugen Liu
Summary: The neural retina leucine zipper (NRL) gene plays a crucial role in the development and maintenance of rod photoreceptors in mammals. This study aimed to determine the role of Nrl in zebrafish and found that the loss of Nrl resulted in a reduced number of rods and over-growth of green cones. The study also identified the mafba gene as a regulator of rod development independent of Nrl. The altered photoreceptor composition and abnormal gene expression in Nrl mutants caused retinal degeneration and subsequent regeneration.
Article
Cell & Tissue Engineering
Devansh Agarwal, Nicholas Dash, Kevin W. Mazo, Manan Chopra, Maria P. Avila, Amit Patel, Ryan M. Wong, Cairang Jia, Hope Do, Jie Cheng, Colette Chiang, Shawna L. Jurlina, Mona Roshan, Michael W. Perry, Jong M. Rho, Risa Broyer, Cassidy D. Lee, Robert N. Weinreb, Cezar Gavrilovici, Nicholas W. Oesch, Derek S. Welsbie, Karl J. Wahlin
Summary: This study explores cellular reprogramming using transcription factor regulations to convert human pluripotent stem cells into induced neurons similar to retinal ganglion cells. It also demonstrates the potential of small molecule inhibitors to block neuronal death and provides valuable insights for cell replacement and neuroprotection strategies.
NPJ REGENERATIVE MEDICINE
(2023)
Article
Neurosciences
Shun Masuda, Shigeru Tanaka, Hiroko Shiraki, Yusuke Sotomaru, Kana Harada, Izumi Hide, Yoshiaki Kiuchi, Norio Sakai
Summary: The expression of GPR3 in retinal ganglion cells (RGCs) plays an important role in axonal regeneration and neuronal survival. Knocking out the GPR3 gene makes RGCs more vulnerable to neural death, while upregulation of GPR3 accelerates axonal regeneration.
NEUROBIOLOGY OF DISEASE
(2022)
Article
Biology
Michelle C. Stone, Abigail S. Mauger, Melissa M. Rolls
Summary: Axon regeneration is crucial for maintaining the lifelong function of neurons. This study investigates the ability of ciliated sensory neurons to grow new axons after proximal axon injury. The results show that these neurons are not intrinsically limited in their ability to regenerate axons, and neurites can regrow in various forms after injury. The findings shed light on the flexibility and potential of ciliated sensory neurons in responding to axon damage.
JOURNAL OF EXPERIMENTAL BIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Xiu-Qing Fu, Wen-Rong Zhan, Wei-Ya Tian, Dong-Dong Cao, Zhen-Ge Luo
Summary: The nervous system is composed of different types of neurons and glial cells, and neurons have varying regenerative abilities. Comparative studies of axonal regeneration among different cell subtypes in different animal models or the same organ can help identify key factors that promote regeneration.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2022)
Article
Clinical Neurology
Yueming Song, Limin Guo, Xingxiong Jiang, Minglin Dong, Dong Xiang, Ming Wen, Shaoxuan He, Yong Yuan, Feng Lin, Gang Zhao, Luping Liu, Jingwu Liao
Summary: This study investigates the effects of the cAMP analog meglumine cyclic adenylate (MCA) on cardiovascular and neurological recovery in rats with acute spinal cord injury (SCI). The results demonstrate that MCA significantly reverses the decrease in cAMP levels, improves hypotension, bradycardia and behavioral parameters, and enhances spinal cord blood flow and histological structure after SCI. Therefore, MCA may be an effective treatment for acute SCI.
Review
Biochemistry & Molecular Biology
Supraja G. Varadarajan, John L. Hunyara, Natalie R. Hamilton, Alex L. Kolodkin, Andrew D. Huberman
Summary: This article summarizes the research progress on neuronal regeneration and degeneration, compares the regenerative process in the central and peripheral nervous systems, and highlights the primary targets for restoring functional neural circuits.
Article
Clinical Neurology
Guy M. Lenk, Paymaan Jafar-Nejad, Sophie F. Hill, Lucas D. Huffman, Corrine E. Smolen, Jacy L. Wagnon, Hayley Petit, Wenxi Yu, Julie Ziobro, Kritika Bhatia, Jack Parent, Roman J. Giger, Frank Rigo, Miriam H. Meisler
ANNALS OF NEUROLOGY
(2020)
Article
Urology & Nephrology
Virginie Royal, Jarcy Zee, Qian Liu, Carmen Avila-Casado, Abigail R. Smith, Gang Liu, Laura H. Mariani, Stephen Hewitt, Lawrence B. Holzman, Brenda W. Gillespie, Jeffrey B. Hodgin, Laura Barisoni
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2020)
Article
Cell Biology
Patricia M. Garay, Alex Chen, Takao Tsukahara, Jean Carlos Rodriguez Diaz, Rafi Kohen, J. Christian Althaus, Margarete A. Wallner, Roman J. Giger, Kevin S. Jones, Michael A. Sutton, Shigeki Iwase
Article
Urology & Nephrology
Catherine P. Jayapandian, Yijiang Chen, Andrew R. Janowczyk, Matthew B. Palmer, Clarissa A. Cassol, Miroslav Sekulic, Jeffrey B. Hodgin, Jarcy Zee, Stephen M. Hewitt, John O'Toole, Paula Toro, John R. Sedor, Laura Barisoni, Anant Madabhushi
Summary: The application of deep learning for automated segmentation of histologic structures from kidney biopsies and nephrectomies showed that Periodic Acid Schiff-stained whole slide images yielded the best concordance between pathologists and deep learning segmentation. Silver stained whole slide images yielded the worst deep learning performance. This study represents the largest adaptation of deep learning for the segmentation of kidney histologic structures across multiple stains and pathology laboratories.
KIDNEY INTERNATIONAL
(2021)
Article
Immunology
Andrew R. Sas, Kevin S. Carbajal, Andrew D. Jerome, Rajasree Menon, Choya Yoon, Ashley L. Kalinski, Roman J. Giger, Benjamin M. Segal
Article
Biology
Ashley L. Kalinski, Choya Yoon, Lucas D. Huffman, Patrick C. Duncker, Rafi Kohen, Ryan Passino, Hannah Hafner, Craig Johnson, Riki Kawaguchi, Kevin S. Carbajal, Juan Sebastian Jara, Edmund Hollis, Daniel H. Geschwind, Benjamin M. Segal, Roman J. Giger
Article
Pediatrics
Jarcy Zee, Michelle T. McNulty, Jeffrey B. Hodgin, Olga Zhdanova, Sangeeta Hingorani, Jonathan Ashley Jefferson, Keisha L. Gibson, Howard Trachtman, Alessia Fornoni, Katherine M. Dell, Heather N. Reich, Serena Bagnasco, Larry A. Greenbaum, Richard A. Lafayette, Debbie S. Gipson, Elizabeth Brown, Matthias Kretzler, Gerald Appel, Kamalanathan K. Sambandam, Katherine R. Tuttle, Dhruti Chen, Meredith A. Atkinson, Marie C. Hogan, Frederick J. Kaskel, Kevin E. Meyers, John O'Toole, Tarak Srivastava, Christine B. Sethna, Michelle A. Hladunewich, J. J. Lin, Cynthia C. Nast, Vimal K. Derebail, Jiten Patel, Suzanne Vento, Lawrence B. Holzman, Ambarish M. Athavale, Sharon G. Adler, Kevin Lemley, John C. Lieske, Jonathan J. Hogan, Crystal A. Gadegbeku, Fernando C. Fervenza, Chia-Shi Wang, Raed Bou Matar, Pamela Singer, Jeffrey B. Kopp, Laura Barisoni, Matthew G. Sampson
Summary: In this study, APOL1 risk variants were significantly associated with certain tissue changes in FSGS patients, while no significant correlations were found in the MCD cohort. This suggests that both one and two risk alleles may be associated with cellular/tissue changes in FSGS.
PEDIATRIC NEPHROLOGY
(2021)
Editorial Material
Biochemistry & Molecular Biology
Jeffery L. Twiss, Ashley L. Kalinski, Pabitra K. Sahoo, Irene Dalla Costa, Roman J. Giger
Summary: Neuronal injury can lead to mitochondrial damage, affecting energy production and Ca2+ storage while increasing reactive oxygen species. A new study has identified a mechanism to promote neuroprotection and axon regeneration by facilitating axonal transport of mitochondria and replacing damaged ones with functional ones.
Article
Multidisciplinary Sciences
Dhananjay Yellajoshyula, Samuel S. Pappas, Abigail E. Rogers, Biswa Choudhury, Xylena Reed, Jinhui Ding, Mark R. Cookson, Vikram G. Shakkottai, Roman J. Giger, William T. Dauer
Summary: THAP1 regulates myelination initiation by modulating GAG catabolism and ECM composition, with a lack of THAP1 leading to excess GAG accumulation and inhibition of OL maturation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Neurosciences
Tao Yang, Macy W. Veling, Xiao-Feng Zhao, Nicholas P. Prin, Limei Zhu, Ty Hergenreder, Hao Liu, Lu Liu, Zachary S. Rane, Masha G. Savelieff, Peter G. Fuerst, Qing Li, Kenneth Y. Kwan, Roman J. Giger, Yu Wang, Bing Ye
Summary: This study reveals the importance of Down syndrome cell adhesion molecule (DSCAM) in the migration of neurons during neocortex development. DSCAM is required for migrating neurons to bypass their predecessors and reach their final positions. The mechanism involves weakening cell adhesion mediated by N-cadherin.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Multidisciplinary Sciences
Robert Doherty, Brenna L. MacLeod, Megan M. Nelson, Mostafa M. H. Ibrahim, Beatriz C. Borges, Nada W. Jaradat, Matthew C. Finneran, Roman J. Giger, Gabriel Corfas
Summary: ErbB4 is a receptor tyrosine kinase that signals through both canonical phosphorylation cascades and a non-canonical mechanism involving intramembrane proteolysis. Its signaling depends on alternative spliced isoforms, including RIP cleavable ErbB4-JMa and uncleavable ErbB4-JMb. This study demonstrates the importance of non-canonical ErbB4-JMa signaling in regulating GFAP expression during cortical development, while not being essential for the development of other organs. It also identifies specific genes that are regulated by ErbB4 and shows that their expression depends on either ErbB4-JMa or ErbB4-JMb.
SCIENTIFIC REPORTS
(2022)
Article
Biology
Justine M. Pinskey, Tyler M. Hoard, Xiao-Feng Zhao, Nicole E. Franks, Zoe C. Frank, Alexandra N. McMellen, Roman J. Giger, Benjamin L. Allen
Summary: Hedgehog signaling is crucial throughout the life of an organism, and this study reveals Plexin as a novel component of this pathway and investigates its functionality and mechanism of action.
Correction
Multidisciplinary Sciences
Robert Doherty, Brenna L. MacLeod, Megan M. Nelson, Mostafa M. H. Ibrahim, Beatriz C. Borges, Nada W. Jaradat, Matthew C. Finneran, Roman J. Giger, Gabriel Corfas
SCIENTIFIC REPORTS
(2022)
Article
Biology
Xiao-Feng Zhao, Lucas D. Huffman, Hannah Hafner, Mitre Athaiya, Matthew C. Finneran, Ashley L. Kalinski, Rafi Kohen, Corey Flynn, Ryan Passino, Craig N. Johnson, David Kohrman, Riki Kawaguchi, Lynda J. S. Yang, Jeffery L. Twiss, Daniel H. Geschwind, Gabriel Corfas, Roman J. Giger
Summary: This study performed single-cell analysis to investigate the pathological changes following nerve injury in mice. It was found that macrophages rapidly accumulated at the site of nerve injury and underwent metabolic reprogramming. The blood-nerve barrier showed partial leakiness, resulting in proliferation of stromal cells and entry of serum proteins. Distinct immune compartments were identified in response to mechanical nerve injury and Wallerian degeneration. Delayed Wallerian degeneration affected the distribution of immune cells in both the injured nerve and the distal nerve.
Article
Urology & Nephrology
Jonathan P. Troost, Anne Waldo, Noelle E. Carlozzi, Shannon Murphy, Frank Modersitzki, Howard Trachtman, Patrick H. Nachman, Kimberly J. Reidy, David T. Selewski, Emily G. Herreshoff, Tarak Srivastava, Keisha L. Gibson, Vimal K. Derebail, Jen Jar Lin, Sangeeta Hingorani, Alessia Fornoni, Fernando C. Fervenza, Kamalanathan Sambandam, Ambarish M. Athavale, Jeffrey B. Kopp, Heather N. Reich, Sharon G. Adler, Larry A. Greenbaum, Katherine M. Dell, Gerald Appel, Chia-shi Wang, John Sedor, Frederick J. Kaskel, Richard A. Lafayette, Meredith A. Atkinson, John C. Lieske, Christine B. Sethna, Matthias Kretzler, Michelle A. Hladunewich, Kevin Lemley, Elizabeth Brown, Kevin E. Meyers, Crystal A. Gadegbeku, Lawrence B. Holzman, Jonathan Ashley Jefferson, Katherine R. Tuttle, Pamela Singer, Marie C. Hogan, Daniel C. Cattran, Laura Barisoni, Debbie S. Gipson
CLINICAL KIDNEY JOURNAL
(2020)
