Central nervous system (CNS) neurons typically fail to regrow their axons after injury. Injuries or neuropathies that damage CNS axons and disrupt neuronal circuitry often result in permanent functional deficits. Axon regeneration is therefore an intensely pursued therapeutic strategy for numerous CNS disorders. Phenotypic screens utilizing primary neurons have proven successful at identifying agents that promote axon regeneration . Here, we report the screening of mixture-based combinatorial small molecule libraries in a phenotypic assay utilizing primary CNS neurons and the discovery of neurite outgrowth promoters with low nanomolar potency.
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http://dx.doi.org/10.1021/acsmedchemlett.8b00425 | DOI Listing |
bioRxiv
January 2025
Department of Biology, University of Iowa, Iowa City, IA 52242 USA.
Neurotrophic factors are critical for establishing functional connectivity in the nervous system and sustaining neuronal survival through adulthood. As the first neurotrophic factor purified, nerve growth factor (NGF) is extensively studied for its prolific role in axon outgrowth, pruning, and survival. Applying NGF to diseased neuronal tissue is an exciting therapeutic option and understanding how NGF regulates local axon susceptibility to pathological degeneration is critical for exploiting its full potential.
View Article and Find Full Text PDFEndocrinology
January 2025
Graduate Program in Cellular and Molecular Biology.
SH2B1β is a multifunctional scaffold protein that modulates cytoskeletal processes such as cellular motility and neurite outgrowth. To identify novel SH2B1β-interacting proteins involved in these processes, a yeast two-hybrid assay was performed. The C-terminal 159 residues of the cytoskeleton structural protein, βIIΣ1-spectrin, interacted with the N-terminal 260 residues of SH2B1β, a region implicated in SH2B1β enhancement of cell motility and localization at the plasma membrane.
View Article and Find Full Text PDFEur J Med Chem
January 2025
Medical Research Center, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong, China. Electronic address:
The development of potent glycogen synthase kinase-3β (GSK-3β) inhibitor has been increasingly recognized as the candidate treatment against the multifactorial pathogenic mechanism of Alzheimer's disease (AD). This study prepared various new pyrrolo[2,3-b]pyridine derivatives, evaluated the anti-AD activities and detected the security based on the structure-guided rational design. Our results indicated that many pyrrolo[2,3-b]pyridine derivatives had strong GSK-3β inhibitory activities, particularly compounds 41, 46 and 54, with the half maximal inhibitory concentrations (IC) of 0.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Department of Orthopedic Surgery, E-Da Hospital, I-Shou University, Kaohsiung City 824, Taiwan.
Olfactory ensheathing cell (OEC) transplantation demonstrates promising therapeutic results in neurological disorders, such as spinal cord injury. The emerging cell-free secretome therapy compensates for the limitations of cell transplantation, such as low cell survival rates. However, the therapeutic benefits of the human OEC secretome remain unclear.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Shenzhen Key Laboratory of Neuroimmunomodulation for Neurological Diseases, Shenzhen-Hong Kong Institute of Brain Science, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
Induced pluripotent stem cell (iPSC)-derived neurons (iNs) have been widely used as models of neurodevelopment and neurodegenerative diseases. Coating cell culture vessels with extracellular matrixes (ECMs) gives structural support and facilitates cell communication and differentiation, ultimately enhances neuronal functions. However, the relevance of different ECMs to the natural environment and their impact on neuronal differentiation have not been fully characterized.
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