Nuclear pore dysfunction and disease: a complex opportunity

Autor: Charlotte M. Fare, Jeffrey D. Rothstein

Publikováno v: Nucleus, Vol 15, Iss 1 (2024)

The separation of genetic material from bulk cytoplasm has enabled the evolution of increasingly complex organisms, allowing for the development of sophisticated forms of life. However, this complexity has created new categories of dysfunction, inclu

Externí odkaz: https://doaj.org/article/2c12c367ce224c1fba66e78eb8f949c3

A Phase 1 study of GDC‐0134, a dual leucine zipper kinase inhibitor, in ALS

Autor: Jonathan S. Katz, Jeffrey D. Rothstein, Merit E. Cudkowicz, Angela Genge, Björn Oskarsson, Avis B. Hains, Chen Chen, Joshua Galanter, Braydon L. Burgess, William Cho, Geoffrey A. Kerchner, Felix L. Yeh, Arundhati Sengupta Ghosh, Sravanthi Cheeti, Logan Brooks, Lee Honigberg, Jessica A. Couch, Michael E. Rothenberg, Flavia Brunstein, Khema R. Sharma, Leonard van denBerg, James D. Berry, Jonathan D. Glass

Publikováno v: Annals of Clinical and Translational Neurology, Vol 9, Iss 1, Pp 50-66 (2022)

Abstract Objective Dual leucine zipper kinase (DLK), which regulates the c‐Jun N‐terminal kinase pathway involved in axon degeneration and apoptosis following neuronal injury, is a potential therapeutic target in amyotrophic lateral sclerosis (AL

Externí odkaz: https://doaj.org/article/fe4980573fc74660b0489437b3effc6d

The ESCRT-III protein VPS4, but not CHMP4B or CHMP2B, is pathologically increased in familial and sporadic ALS neuronal nuclei

Autor: Alyssa N. Coyne, Jeffrey D. Rothstein

Publikováno v: Acta Neuropathologica Communications, Vol 9, Iss 1, Pp 1-9 (2021)

Abstract Nuclear pore complex injury has recently emerged as an early and significant contributor to familial and sporadic ALS disease pathogenesis. However, the molecular events leading to this pathological phenomenon characterized by the reduction

Externí odkaz: https://doaj.org/article/97f27762a1224de6b81059ac16a83487

Identification of Therapeutic Targets for Amyotrophic Lateral Sclerosis Using PandaOmics – An AI-Enabled Biological Target Discovery Platform

Autor: Frank W. Pun, Bonnie Hei Man Liu, Xi Long, Hoi Wing Leung, Geoffrey Ho Duen Leung, Quinlan T. Mewborne, Junli Gao, Anastasia Shneyderman, Ivan V. Ozerov, Ju Wang, Feng Ren, Alexander Aliper, Evelyne Bischof, Evgeny Izumchenko, Xiaoming Guan, Ke Zhang, Bai Lu, Jeffrey D. Rothstein, Merit E. Cudkowicz, Alex Zhavoronkov

Publikováno v: Frontiers in Aging Neuroscience, Vol 14 (2022)

Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease with ill-defined pathogenesis, calling for urgent developments of new therapeutic regimens. Herein, we applied PandaOmics, an AI-driven target discovery platform, to analyze th

Externí odkaz: https://doaj.org/article/d12999749a99465fb2c046587d7bb7ef

An integrated multi-omic analysis of iPSC-derived motor neurons from C9ORF72 ALS patients

Autor: Jonathan Li, Ryan G. Lim, Julia A. Kaye, Victoria Dardov, Alyssa N. Coyne, Jie Wu, Pamela Milani, Andrew Cheng, Terri G. Thompson, Loren Ornelas, Aaron Frank, Miriam Adam, Maria G. Banuelos, Malcolm Casale, Veerle Cox, Renan Escalante-Chong, J. Gavin Daigle, Emilda Gomez, Lindsey Hayes, Ronald Holewenski, Susan Lei, Alex Lenail, Leandro Lima, Berhan Mandefro, Andrea Matlock, Lindsay Panther, Natasha Leanna Patel-Murray, Jacqueline Pham, Divya Ramamoorthy, Karen Sachs, Brandon Shelley, Jennifer Stocksdale, Hannah Trost, Mark Wilhelm, Vidya Venkatraman, Brook T. Wassie, Stacia Wyman, Stephanie Yang, Jennifer E. Van Eyk, Thomas E. Lloyd, Steven Finkbeiner, Ernest Fraenkel, Jeffrey D. Rothstein, Dhruv Sareen, Clive N. Svendsen, Leslie M. Thompson, Hemali Phatnani, PhD, Justin Kwan, MD, Dhruv Sareen, PhD, James R. Broach, PhD, Zachary Simmons, MD, Ximena Arcila-Londono, MD, Edward B. Lee, MD, PhD, Vivianna M. Van Deerlin, MD, PhD, Neil A. Shneider, MD, PhD, Ernest Fraenkel, PhD, Lyle W. Ostrow, MD, PhD, Frank Baas, MD, PhD, Noah Zaitlen, PhD, James D. Berry, MD, MPH, Andrea Malaspina, MD, PhD, Pietro Fratta, MD, PhD, Gregory A. Cox, PhD, Leslie M. Thompson, PhD, Steve Finkbeiner, MD, PhD, Efthimios Dardiotis, MD, PhD, Timothy M. Miller, MD, PhD, Siddharthan Chandran, PhD, Suvankar Pal, MD, Eran Hornstein, MD, PhD, Daniel J. MacGowan, MD, Terry Heiman-Patterson, MD, Molly G. Hammell, PhD, Nikolaos.A. Patsopoulos, MD, PhD, Oleg Butovsky, PhD, Joshua Dubnau, PhD, Avindra Nath, MD, Robert Bowser, PhD, Matt Harms, MD, Mary Poss, DVM, PhD, Jennifer Phillips-Cremins, PhD, John Crary, MD, PhD, Nazem Atassi, MD, Dale J. Lange, MD, Darius J. Adams, MD, Leonidas Stefanis, MD, PhD, Marc Gotkine, MD, Robert H. Baloh, MD. PhD, Suma Babu, MBBS, MPH, Towfique Raj, PhD, Sabrina Paganoni, MD, PhD, Ophir Shalem, PhD, Colin Smith, MD, Bin Zhang, PhD, Brent Harris, MD, PhD, Iris Broce, PhD, Vivian Drory, MD, John Ravits, MD, Corey McMillan, PhD, Vilas Menon, PhD, Lani Wu, PhD, Steven Altschuler, PhD

Publikováno v: iScience, Vol 24, Iss 11, Pp 103221- (2021)

Summary: Neurodegenerative diseases are challenging for systems biology because of the lack of reliable animal models or patient samples at early disease stages. Induced pluripotent stem cells (iPSCs) could address these challenges. We investigated D

Externí odkaz: https://doaj.org/article/b0aa201abf104ba08a6430dac01837c5