Article
Radiology, Nuclear Medicine & Medical Imaging
Hanyi Fang, Samantha Rossano, Xingxing Wang, Nabeel Nabulsi, Brian Kelley, Krista Fowles, Jim Ropchan, Stephen M. Strittmatter, Richard E. Carson, Yiyun Huang
Summary: The study investigated the potential use of PET imaging with SERT radioligand [C-11]AFM as a biomarker for axon damage after spinal cord injury (SCI). The results showed that the [C-11]AFM PET imaging method could effectively visualize the rodent spinal cord and detect SERT changes in SCI rodent models. However, there was limited specific binding signal for [C-11]AFM in the human spinal cord, indicating the need for a tracer with higher affinity and lower non-specific binding signal for imaging the spinal cord in humans and assessing axonal status in SCI patients.
MOLECULAR IMAGING AND BIOLOGY
(2022)
Article
Neurosciences
Daniel Franjic, Mario Skarica, Shaojie Ma, Jon Arellano, Andrew T. N. Tebbenkamp, Jinmyung Choi, Chuan Xu, Qian Li, Yury M. Morozov, David Andrijevic, Zvonimir Vrselja, Ana Spajic, Gabriel Santpere, Mingfeng Li, Shupei Zhang, Yang Liu, Joshua Spurrier, Le Zhang, Ivan Gudelj, Lucija Rapan, Hideyuki Takahashi, Anita Huttner, Rong Fan, Stephen M. Strittmatter, Andre M. M. Sousa, Pasko Rakic, Nenad Sestan
Summary: The hippocampal-entorhinal system supports cognitive functions and has neurogenic capabilities in many species. This study profiled the single-nucleus transcriptomes in different subregions of the hippocampal-entorhinal system in humans, macaques, and pigs. The findings revealed species differences in neurogenesis and cellular diversity, as well as the association between certain proteins and Alzheimer's disease.
Article
Neurosciences
A. Harrison Brody, Sarah Helena Nies, Fulin Guan, Levi M. Smith, Bandhan Mukherjee, Santiago A. Salazar, Suho Lee, Tu Kiet T. Lam, Stephen M. Strittmatter
Summary: The presence of Pyk2 protein affects the phosphorylation of Tau protein and the activity of protein kinases, which in turn influences Alzheimer's disease. The absence of Pyk2 exacerbates pathological features related to Tau in mouse models.
MOLECULAR NEURODEGENERATION
(2022)
Review
Neurosciences
Lauren K. Wareham, Shane A. Liddelow, Sally Temple, Larry Benowitz, Adriana Di Polo, Cheryl Wellington, Jeffrey L. Goldberg, Zhigang He, Xin Duan, Guojun Bu, Albert A. Davis, Karthik Shekhar, Anna La Torre, David C. Chan, M. Valeria Canto-Soler, John G. Flanagan, Preeti Subramanian, Sharyn Rossi, Thomas Brunner, Diane E. Bovenkamp, David J. Calkins
Summary: There may be common mechanisms across neurodegenerative diseases that can lead to new therapeutic targets. A virtual meeting was organized to discuss these mechanisms and emerging treatments. The meeting focused on neuroinflammation, bioenergetics and metabolism, genetic contributions, and neurovascular interactions as major areas of mechanistic overlap.
MOLECULAR NEURODEGENERATION
(2022)
Editorial Material
Multidisciplinary Sciences
Hideyuki Takahashi, Stephen M. Strittmatter
Summary: Protein fibrils are known to accumulate in the brain during neurodegeneration, and now cryo-electron microscopy has revealed the high-resolution structures of TMEM106B fibrils, which were not previously thought to accumulate.
Article
Multidisciplinary Sciences
Lili Xie, Ling-Ping Cen, Yiqing Li, Hui-Ya Gilbert, Oleksandr Strelko, Cynthia Berlinicke, Mihaela A. Stavarache, Madeline Ma, Yongting Wang, Qi Cui, Michael G. Kaplitt, Donald J. Zack, Larry I. Benowitz, Yuqin Yin
Summary: Sterile inflammation in the eye can partially reverse the failure of mammalian retinal ganglion cells (RGCs) to regenerate axons and survive after optic nerve injury. This reversal is mediated by the expression of axogenic protein oncomodulin (Ocm) by infiltrative myeloid cells. Additionally, stromal cell-derived factor 1 (SDF1) expressed by infiltrative macrophages plays a central role in enhancing Ocm activity and promoting inflammation-induced regeneration and RGC survival.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Yuyan Cheng, Yuqin Yin, Alice Zhang, Alexander M. Bernstein, Riki Kawaguchi, Kun Gao, Kyra Potter, Hui-Ya Gilbert, Yan Ao, Jing Ou, Catherine J. Fricano-Kugler, Jeffrey L. Goldberg, Zhigang He, Clifford J. Woolf, Michael V. Sofroniew, Larry I. Benowitz, Daniel H. Geschwind
Summary: In this study, the authors used integrative genomic analysis and experimental validation to identify REST as a novel suppressor of a pro-regenerative gene program and CNS axon regeneration in mice. They demonstrated the inhibitory role of REST and highlighted the importance of a systems biology approach in CNS repair.
NATURE COMMUNICATIONS
(2022)
Review
Biochemistry & Molecular Biology
Kimberly A. Wong, Larry I. Benowitz
Summary: The optic nerve, once injured, cannot regenerate, leading to the death of retinal ganglion cells. However, research has identified strategies that can enable regeneration and improve vision, offering hope for patients with currently untreatable losses.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Correction
Neurosciences
A. Harrison Brody, Sarah Helena Nies, Fulin Guan, Levi M. Smith, Bandhan Mukherjee, Santiago A. Salazar, Suho Lee, Tu Kiet T. Lam, Stephen M. Strittmatter
MOLECULAR NEURODEGENERATION
(2022)
Article
Multidisciplinary Sciences
Shaojie Ma, Mario Skarica, Qian Li, Chuan Xu, Ryan D. Risgaard, Andrew T. N. Tebbenkamp, Xoel Mato-Blanco, Rothem Kovner, Zeljka Krsnik, Xabier de Martin, Victor Luria, Xavier Marti-Perez, Dan Liang, Amir Karger, Danielle K. Schmidt, Zachary Gomez-Sanchez, Cai Qi, Kevin T. Gobeske, Sirisha Pochareddy, Ashwin Debnath, Cade J. Hottman, Joshua Spurrier, Leon Teo, Anthony G. Boghdadi, Jihane Homman-Ludiye, John J. Ely, Etienne W. Daadi, Da Mi, Marcel Daadi, Oscar Marin, Patrick R. Hof, Mladen-Roko Rasin, James Bourne, Chet C. Sherwood, Gabriel Santpere, Matthew J. Girgenti, Stephen M. Strittmatter, Andre M. M. Sousa, Nenad Sestan
Summary: The study reveals species-specific molecular differences in the cellular composition of the dorsolateral prefrontal cortex (dlPFC) among humans, chimpanzees, macaques, and marmosets, including expression switches in certain cell subtypes and the presence of unique expression patterns of neuropsychiatric risk genes.
Article
Multidisciplinary Sciences
Takahiko Noro, Sahil H. Shah, Yuqin Yin, Riki Kawaguchi, Satoshi Yokota, Kun-Che Chang, Ankush Madaan, Catalina Sun, Giovanni Coppola, Daniel Geschwind, Larry Benowitz, Jeffrey L. Goldberg
Summary: This study analyzed the transcriptomes of retinal ganglion cells after optic nerve injury and discovered Elk-1 as the top regulator of RGC gene expression associated with axon outgrowth. Manipulating phosphorylation sites enhanced Elk-1's role in promoting neuroprotection and regeneration. Additionally, PTEN and REST were found to regulate Elk-1 in the survival and axon regenerative pathway in RGCs.
SCIENTIFIC REPORTS
(2022)
Article
Cell Biology
Caitlin M. Rodriguez, Sophia C. Bechek, Graham L. Jones, Lisa Nakayama, Tetsuya Akiyama, Garam Kim, David E. Solow-Cordero, Stephen M. Strittmatter, Aaron D. Gitler
Summary: Gene-based therapeutic strategies to lower ataxin-2 levels are emerging for ALS and SCA2. This study identifies RTN4R as a potent modifier of ataxin-2 levels, and demonstrates that reducing RTN4R expression or using a peptide inhibitor can lower ataxin-2 protein levels. Additionally, it is found that both ataxin-2 and RTN4/NoGo-Receptor play a role in limiting axonal regeneration.
Article
Clinical Neurology
Chao Zheng, Takuya Toyonaga, Baosheng Chen, LaShae Nicholson, William Mennie, Michael Liu, Joshua Spurrier, Kristin Deluca, Stephen M. Strittmatter, Richard E. Carson, Yiyun Huang, Zhengxin Cai
Summary: In this study, the novel SV2A PET imaging probe [F-18]SDM-16 was used to detect decreased SV2A levels in the brain of APP/PS1 AD mouse model. The results showed that [F-18]SDM-16 had similar statistical power in detecting synapse loss as other imaging probes.
FRONTIERS IN NEUROLOGY
(2023)
Article
Medicine, Research & Experimental
Qian Feng, Kimberly A. Wong, Larry I. Benowitz
Summary: The inability of retinal ganglion cells (RGCs) to regenerate axons after optic nerve injury can be partially reversed by manipulating cell-autonomous and/or non-autonomous factors. Preconditioning resulting from mild lens injury before optic nerve damage induced greater regeneration than other interventions. The findings suggest that non-autonomous interventions can induce high levels of optic nerve regeneration, providing potential therapeutic targets for CNS repair.
Article
Cell Biology
Lili Xie, Yuqin Yin, Selwyn Jayakar, Riki Kawaguchi, Qing Wang, Sheri Peterson, Caleb Shi, Bruna Lenfers Turnes, Zihe Zhang, Juan Oses-Prieto, Jian Li, Al Burlingame, Clifford J. Woolf, Daniel Geschwind, Matthew Rasband, Larry I. Benowitz
Summary: By using various techniques, including proximity biotinylation and coimmunoprecipitation, researchers have identified ArmC10 as a high-affinity receptor for Ocm, a growth factor that promotes axon regeneration. Deletion of ArmC10 suppresses axon regeneration in mice with optic nerve injury and attenuates the conditioning lesion effect. On the other hand, Ocm promotes nerve regeneration through ArmC10 in various nerve injury models. These findings suggest that targeting Ocm and its receptor ArmC10 may have therapeutic potential for nerve repair and immune modulation.
SCIENCE TRANSLATIONAL MEDICINE
(2023)