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The conversion of non-neuronal cells to neurons is a promising potential strategy for the treatment of neurodegenerative diseases. Recent studies have reported that shRNA-, CasRx-, or ASO-mediated Ptbp1 suppression could reprogram resident astrocytes to neurons. However, some groups have disputed the interpretation of the data underlying the reported neuron conversion events. These controversies surrounding neuron conversion may be due to differences in the astrocyte fate-mapping systems. Here, we suppressed Ptbp1 using Cas13X and labelled astrocytes with an HA tag fused to Cas13X (Cas13X-NLS-HA). We found no astrocyte-to-neuron conversion in the mouse striatum via the HA-tagged labelling system compared with the GFAP-driven tdTomato labelling system (AAV-GFAP::tdTomato-WPRE) used in previous studies. Our findings indicate that Cas13X-mediated Ptbp1 knockdown failed to induce neuron conversion in vivo.
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http://dx.doi.org/10.1038/s41434-023-00382-5 | DOI Listing |
Ecotoxicol Environ Saf
September 2025
Department of Orthordontics, School and Hospital of Stomatology, Guangdong Engineering Research Center of Oral Restoration and Reconstruction & Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou Medical University, Guangzhou, China. Electronic address: 20
Nanomaterials are widely used. The gases emitted from industrial manufacturing contain nanoparticles, which increases the chance of nanomaterials coming into contact with the eyes. Nanomaterials may cause damage to the eyeball wall and eye contents, manifested as keratitis, neovascularization of the iris, vitreous inflammation, retinitis, etc.
View Article and Find Full Text PDFCell Rep
September 2025
Department of Chemical Engineering, MIT, Cambridge, MA 02139, USA. Electronic address:
Cell states evolve through the combined activity of signaling pathways and gene networks. While transcription factors can direct cell fate, these factors rely on a receptive cell state. How signaling levels contribute to the emergence of receptive cell states remains poorly defined.
View Article and Find Full Text PDFInt Immunopharmacol
September 2025
Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address:
Background: To elucidate the therapeutic effects and underlying mechanisms of palmatine, a principal alkaloid derived from Coptis chinensis, on neuroinflammation in ischemic stroke rat models induced by middle cerebral artery occlusion (MCAO).
Methods: Initially, qPCR was employed to assess the impact of neurotrophic factors secreted by SH-SY5Y neuroblastoma cells on the phenotypes of BV2 cells. Alterations in sphingolipid profiles within neuronal supernatants were characterized using liquid chromatography-tandem mass spectrometry, and molecular docking studies were conducted to investigate the interaction of palmatine with key enzymes involved in sphingolipid metabolism.
bioRxiv
August 2025
Department of Biochemistry & Biophysics, Weill Cornell Medicine, New York, NY.
The brain is a metabolically vulnerable organ as neurons have both high resting metabolic rates and the need for local rapid conversion of carbon sources to ATP during activity. Midbrain dopamine neurons are thought to be particularly vulnerable to metabolic perturbations, as a subset of these are the first to undergo degeneration in Parkinson's disease (PD), a neurodegenerative disorder long suspected to be in part driven by deficits in mid-brain bioenergetics (1). In skeletal muscle, energy homeostasis under varying demands is achieved in part by its ability to rely on glycogen as a fuel store, whose conversion to ATP is under hormonal regulatory control.
View Article and Find Full Text PDFCephalalgia
August 2025
Department of Neurology, NeuroClinic Norway, Lillestrom, Norway.
BackgroundThe discovery of calcitonin gene-related peptide (CGRP) as a key player in migraine pathophysiology has revolutionized the approach to preventive treatment. Atogepant, an oral small-molecule CGRP receptor antagonist, has shown promising efficacy in randomized controlled trials (RCTs) for both episodic and chronic migraine. However, real-world evidence, particularly in individuals with chronic migraine and multiple preventive treatment failures, remains limited.
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