In this issue of Neuron, Shin et al. (2012) show that the dual leucine zipper kinase (DLK) is responsible for the retrograde injury signal in spinal sensory and motor neurons. DLK is required for the accelerated regeneration seen after axotomy and for the improved regeneration seen after a conditioning injury. DLK KO axons have severely reduced axon regeneration in vivo.
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http://dx.doi.org/10.1016/j.neuron.2012.06.005 | DOI Listing |
Nat Commun
December 2024
Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
Currently there are no effective treatments for an array of neurodegenerative disorders to a large part because cell-based models fail to recapitulate disease. Here we develop a reproducible human iPSC-based model where laser axotomy causes retrograde axon degeneration leading to neuronal cell death. Time-lapse confocal imaging revealed that damage triggers an apoptotic wave of mitochondrial fission proceeding from the site of injury to the soma.
View Article and Find Full Text PDFMicroPubl Biol
December 2024
University of California, San Diego, La Jolla, California, United States.
The E3 ubiquitin ligase RPM-1 consists of 3,766 amino acids, with a RING finger domain at the C-terminus that functions to target the DLK-1 kinase for degradation for synapse development and axon termination. for aka F07B7.12 resides 35 kb away from on chromosome V, and is a near-perfect 12 kb duplication of including the entire promoter region and coding sequences.
View Article and Find Full Text PDFInt J Cardiol Congenit Heart Dis
September 2024
Erasmus University Medical Center, Department of Pediatrics, Division of Pediatric Cardiology, Rotterdam, the Netherlands.
Introduction: Patients after surgical correction of Tetralogy of Fallot (ToF) often show adverse cardiac remodeling. To better understand the underlying biological processes, we studied the relation between changes in blood biomarkers and changes in biventricular size and function as assessed by cardiac magnetic resonance imaging (CMR).
Methods: This study included 50 ToF patients, who underwent blood biomarker and CMR analysis at least twice between 2002 and 2018.
Clin Pharmacokinet
December 2024
Clinical Pharmacology and Quantitative Science, Genmab, Plainsboro, NJ, USA.
Background And Objectives: Epcoritamab is a CD3xCD20 bispecific antibody approved for the treatment of adults with different types of relapsed or refractory (R/R) B cell non-Hodgkin lymphoma (B-NHL) after ≥ 2 lines of systemic therapy. Here we report the first results from a population pharmacokinetic model-based analysis using data from 2 phase 1/2 clinical trials (EPCORE NHL-1, NCT03625037 and EPCORE NHL-3, NCT04542824) evaluating epcoritamab in patients with R/R B-NHL.
Methods: Plasma concentration-time data included 6819 quantifiable pharmacokinetic samples from 327 patients with R/R B-NHL.
J Med Chem
December 2024
Schrödinger Inc., San Diego, California 92122, United States.
Dual leucine zipper kinase (DLK), expressed primarily in neuronal cells, is a regulator of neuronal degeneration in response to cellular stress from chronic disease or neuronal injury. This makes it an attractive target for the treatment of neurodegenerative diseases such as Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis, and neuronal injury, such as chemotherapy-induced peripheral neuropathy. Here, we describe the discovery of a potent, selective, brain-penetrant DLK inhibitor, KAI-11101 ().
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