n-Butylidenephthalide recovered calcium homeostasis to ameliorate neurodegeneration of motor neurons derived from amyotrophic lateral sclerosis iPSCs.

Autor: Deng YC; Department of Biochemical and Molecular Medical Sciences, National Dong Hwa University, Hualien, Taiwan.; Everfront Biotech Inc., Taipei, Taiwan., Liu JW; Everfront Biotech Inc., Taipei, Taiwan., Ting HC; Bioinnovation Center, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan., Kuo TC; Department of Biochemical and Molecular Medical Sciences, National Dong Hwa University, Hualien, Taiwan., Chiang CH; Department of Biochemical and Molecular Medical Sciences, National Dong Hwa University, Hualien, Taiwan., Lin EY; Department of Biochemical and Molecular Medical Sciences, National Dong Hwa University, Hualien, Taiwan.; Bioinnovation Center, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan., Harn HJ; Bioinnovation Center, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan.; Department of Pathology, Hualien Tzu Chi Hospital, Hualien, Taiwan., Lin SZ; Bioinnovation Center, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan.; Department of Neurosurgery, Hualien Tzu Chi Hospital, Hualien, Taiwan., Chang CY; Bioinnovation Center, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan.; Department of Nursing, Tzu Chi University of Science and Technology, Hualien, Taiwan.; Department of Medical Research, Hualien Tzu Chi Hospital, Hualien, Taiwan., Chiou TW; Department of Biochemical and Molecular Medical Sciences, National Dong Hwa University, Hualien, Taiwan.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2024 Nov 07; Vol. 19 (11), pp. e0311573. Date of Electronic Publication: 2024 Nov 07 (Print Publication: 2024).
DOI: 10.1371/journal.pone.0311573
Abstrakt: Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease that causes muscle atrophy and primarily targets motor neurons (MNs). Approximately 20% of familial ALS cases are caused by gain-of-function mutations in superoxide dismutase 1 (SOD1), leading to MN degeneration and ion channel dysfunction. Previous studies have shown that n-Butylidenephthalide (BP) delays disease progression and prolongs survival in animal models of ALS. However, no studies have been conducted on models from human sources. Herein, we examined the protective efficacy of BP on MNs derived from induced pluripotent stem cells (iPSCs) of an ALS patient harboring the SOD1G85R mutation as well as on those derived from genetically corrected iPSCs (SOD1G85G). Our results demonstrated that the motor neurons differentiated from iPSC with SOD1G85R mutation exhibited characteristics of neuron degeneration (as indicated by the reduction of neurofilament expression) and ion channel dysfunction (in response to potassium chloride (KCl) and L-glutamate stimulation), in contrast to those derived from the gene corrected iPSC (SOD1G85G). Meanwhile, BP treatment effectively restored calcium ion channel function by reducing the expression of glutamate receptors including glutamate ionotropic receptor AMPA type subunit 3 (GluR3) and glutamate ionotropic receptor NMDA type subunit 1 (NMDAR1). Additionally, BP treatment activated autophagic pathway to attenuate neuron degeneration. Overall, this study supports the therapeutic effects of BP on ALS patient-derived neuron cells, and suggests that BP may be a promising candidate for future drug development.
Competing Interests: The authors declare that they have no competing interests.
(Copyright: © 2024 Deng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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