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This study introduces a novel method for rapidly and efficiently inducing human spinal lower motor neurons (LMNs) from induced pluripotent stem cells (iPSCs) to eventually elucidate the pathomechanisms of amyotrophic lateral sclerosis (ALS) and facilitate drug screening. Previous methods were limited by low induction efficiency, poor LMN purity, or labor-intensive induction and evaluation processes. Our protocol overcomes these challenges, achieving around 80% induction efficiency within just two weeks by combining a small molecule-based approach with transcription factor transduction. Moreover, to exclude non-LMN cells from the analysis, we utilized time-lapse microscopy and machine learning to analyze the morphology and viability of iPSC-derived LMNs on a single-cell basis, establishing an effective pathophysiological evaluation system. This rapid, efficient, and streamlined protocol, along with our single-cell-based evaluation method, enables large-scale analysis and drug screening using iPSC-derived motor neurons.
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http://dx.doi.org/10.1016/j.stemcr.2024.11.007 | DOI Listing |
Eur J Pharmacol
September 2025
Faculty of Medicine, Department of Histology and Embryology, İzmir Katip Çelebi University, İzmir, Turkiye.
Age is the most significant risk factor for Parkinson's disease, a common and progressive neurodegenerative disorder; however, exposure to toxic substances is also strongly implicated. Rotenone, an organic pesticide, induces neuropathological features of Parkinson's disease, and is widely used to create rodent models of the condition. Although the molecular mechanisms involved in the onset and progression of the disease are still unknown, neurodegenerative diseases due to protein accumulation in certain areas of the brain, have been associated with endoplasmic reticulum stress.
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September 2025
Department of Biology, MIT, Cambridge, MA 02139, USA; Department of Brain and Cognitive Sciences, MIT, Cambridge, MA 02139, USA; Picower Institute for Learning and Memory, MIT, Cambridge, MA 02139, USA; Biology of Adversity Project, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Elect
The neural control of breathing is both dynamic and essential, ensuring life-sustaining gas exchange while protecting the respiratory system from harm. Peripheral neurons innervating the respiratory tract exhibit remarkable diversity, continuously relaying sensory feedback to the brain to regulate breathing, trigger protective reflexes such as coughing and sickness behaviors, and even influence emotional states. Understanding this airway-brain axis is especially critical given the increasing global burden of respiratory diseases, as it holds implications for both human health and broader brain-body interactions.
View Article and Find Full Text PDFBiomed Pharmacother
September 2025
Department and Graduate Institute of Pharmacology, College of Pharmacy, National Defense Medical University, Taipei, Taiwan; Department of Pharmacy Practice, Tri-Service General Hospital, National Defense Medical University, Taipei, Taiwan; School of Pharmacy, College of Pharmacy, National Defense M
Parkinson's disease (PD) is characterized by chronic neuroinflammation and progressive dopaminergic neurodegeneration, driven primarily by the activation of microglia and associated apoptotic pathways. The intermediate-conductance calcium-activated potassium channel KCNN4 has recently emerged as a potential therapeutic target, yet its role in chronic neurodegenerative conditions remains underexplored. In this study, we investigated whether pharmacological inhibition of KCNN4 using TRAM-34 can modulate both inflammatory and apoptotic responses in an LPS-induced mouse model of PD.
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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.
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September 2025
Department of Neurosurgery, Stanford University, Stanford, CA 94305, USA; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA; Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA; The Phil & Penny Knight In
The dorsal striatum plays a critical role in action selection, movement, and sensorimotor learning. While action-specific striatal ensembles have been described, the mechanisms underlying their formation and evolution during motor learning remain poorly understood. Here, we employed longitudinal two-photon Ca imaging of dorsal striatal neurons in head-fixed mice as they learned to self-initiate locomotion.
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