keyword
https://read.qxmd.com/read/38608707/parasympathetic-neurons-derived-from-human-pluripotent-stem-cells-model-human-diseases-and-development
#1
JOURNAL ARTICLE
Hsueh-Fu Wu, Kenyi Saito-Diaz, Chia-Wei Huang, Jessica L McAlpine, Dong Eun Seo, D Sumner Magruder, Mohamed Ishan, Harrison C Bergeron, William H Delaney, Fabio R Santori, Smita Krishnaswamy, Gerald W Hart, Ya-Wen Chen, Robert J Hogan, Hong-Xiang Liu, Natalia B Ivanova, Nadja Zeltner
Autonomic parasympathetic neurons (parasymNs) control unconscious body responses, including "rest-and-digest." ParasymN innervation is important for organ development, and parasymN dysfunction is a hallmark of autonomic neuropathy. However, parasymN function and dysfunction in humans are vastly understudied due to the lack of a model system. Human pluripotent stem cell (hPSC)-derived neurons can fill this void as a versatile platform. Here, we developed a differentiation paradigm detailing the derivation of functional human parasymNs from Schwann cell progenitors...
April 4, 2024: Cell Stem Cell
https://read.qxmd.com/read/38608019/neddylation-orchestrates-the-complex-transcriptional-and-posttranscriptional-program-that-drives-schwann-cell-myelination
#2
JOURNAL ARTICLE
Paula Ayuso-García, Alejandro Sánchez-Rueda, Sergio Velasco-Avilés, Miguel Tamayo-Caro, Aroa Ferrer-Pinós, Cecilia Huarte-Sebastian, Vanesa Alvarez, Cristina Riobello, Selene Jiménez-Vega, Izaskun Buendia, Jorge Cañas-Martin, Héctor Fernández-Susavila, Adrián Aparicio-Rey, Eva M Esquinas-Román, Carlos Rodríguez Ponte, Romane Guhl, Nicolas Laville, Encarni Pérez-Andrés, José L Lavín, Monika González-Lopez, Nuria Macías Cámara, Ana M Aransay, Juan José Lozano, James D Sutherland, Rosa Barrio, María Luz Martinez-Chantar, Mikel Azkargorta, Félix Elortza, Mario Soriano-Navarro, Carlos Matute, María Victoria Sánchez-Gómez, Laura Bayón-Cordero, Alberto Pérez-Samartín, Susana B Bravo, Thimo Kurz, Tomas Lama-Díaz, Miguel G Blanco, Saif Haddad, Christopher J Record, Peter M van Hasselt, Mary M Reilly, Marta Varela-Rey, Ashwin Woodhoo
Myelination is essential for neuronal function and health. In peripheral nerves, >100 causative mutations have been identified that cause Charcot-Marie-Tooth disease, a disorder that can affect myelin sheaths. Among these, a number of mutations are related to essential targets of the posttranslational modification neddylation, although how these lead to myelin defects is unclear. Here, we demonstrate that inhibiting neddylation leads to a notable absence of peripheral myelin and axonal loss both in developing and regenerating mouse nerves...
April 12, 2024: Science Advances
https://read.qxmd.com/read/38607045/human-glial-cells-as-innovative-targets-for-the-therapy-of-central-nervous-system-pathologies
#3
REVIEW
Giulia Magni, Benedetta Riboldi, Stefania Ceruti
In vitro and preclinical in vivo research in the last 35 years has clearly highlighted the crucial physiopathological role of glial cells, namely astrocytes/microglia/oligodendrocytes and satellite glial cells/Schwann cells in the central and peripheral nervous system, respectively. Several possible pharmacological targets to various neurodegenerative disorders and painful conditions have therefore been successfully identified, including receptors and enzymes, and mediators of neuroinflammation. However, the translation of these promising data to a clinical setting is often hampered by both technical and biological difficulties, making it necessary to perform experiments on human cells and models of the various diseases...
March 30, 2024: Cells
https://read.qxmd.com/read/38599373/large-cervical-spinal-schwannoma-requiring-anterior-and-posterior-decompression-and-fusion-with-careful-dissection-of-the-vertebral-artery
#4
Omar Hussain, Andrew DeGroot, Randall Treffy, Mohamad Bakhaidar, Joseph Zenga, Saman Shabani
We report a challenging case of a high cervical schwannoma with involvement of the right vertebral artery that could not be sacrificed. We discuss the clinical presentation, surgical approach/techniques, and brief literature review of cervical schwannomas. Our case includes a 58-year-old male referred to neurosurgery due to worsening pain and ataxia, who was found to have a large right sided cervical mass. Early challenges such as C4 vertebral body erosion and vertebral artery encasement were demonstrated on imaging...
April 8, 2024: World Neurosurgery
https://read.qxmd.com/read/38598278/dental-pulp-stem-cell-derived-exosomes-promote-sciatic-nerve-regeneration-via-optimizing-schwann-cell-function
#5
JOURNAL ARTICLE
Ying Chai, Yuemin Liu, Zhiyang Liu, Wenbin Wei, Yabing Dong, Chi Yang, Minjie Chen
Repair strategies for injured peripheral nerve have achieved great progresses in recent years. However, the clinical outcomes remain unsatisfactory. Recent studies have found that exosomes secreted by dental pulp stem cells (DPSC-exos) have great potential for applications in nerve repair. In this study, we evaluated the effects of human DPSC-exos on improving peripheral nerve regeneration. Initially, we established a coculture system between DPSCs and Schwann cells (SCs) in vitro to assess the effect of DPSC-exos on the activity of embryonic dorsal root ganglion neurons (DRGs) growth in SCs...
April 10, 2024: Cellular Reprogramming
https://read.qxmd.com/read/38597449/-mir-132-3p-negatively-regulates-camta1-to-promote-schwann-cell-proliferation-and-migration-and-alleviates-i-125-seeds-induced-exacerbation-of-facial-nerve-injury-in-rats
#6
JOURNAL ARTICLE
J Zhu, X Ouyang, Y Liu, Y Qian, B Xia, Y Shi, L Yu
OBJECTIVE: To investigate the regulatory effect of miR-132-3p on calmodulin-binding transcription activator 1 (CAMTA1) and Schwann cell activity in rats with facial nerve injury (FNI) treated with I-125 seeds. METHODS: Rat Schwann cells were irradiated with I-125 seeds and transfected with miR-132-3p mimic, miR-132-3p inhibitor or sh-CAMTA1. The expressions of S100B and β-tubulin Ⅲ in the cells were detected with immunofluorescence assay, and the expressions of miR-132-3p and CAMTA1 protein were determined using RT-qPCR and Western blotting, respectively...
March 20, 2024: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://read.qxmd.com/read/38595983/conditionally-replicative-adenovirus-as-a-therapy-for-malignant-peripheral-nerve-sheath-tumors
#7
JOURNAL ARTICLE
Julia A Nikrad, Robert T Galvin, Mackenzie M Sheehy, Ethan L Novacek, Kari L Jacobsen, Stanislas M A S Corbière, Pauline J Beckmann, Tyler A Jubenville, Masato Yamamoto, David A Largaespada
Oncolytic adenoviruses (Ads) stand out as a promising strategy for the targeted infection and lysis of tumor cells, with well-established clinical utility across various malignancies. This study delves into the therapeutic potential of oncolytic Ads in the context of neurofibromatosis type 1 (NF1)-associated malignant peripheral nerve sheath tumors (MPNSTs). Specifically, we evaluate conditionally replicative adenoviruses (CRAds) driven by the cyclooxygenase 2 (COX2) promoter, as selective agents against MPNSTs, demonstrating their preferential targeting of MPNST cells compared with non-malignant Schwann cell control...
June 20, 2024: Mol Ther Oncol
https://read.qxmd.com/read/38591541/n-cadherin-directs-the-collective-schwann-cell-migration-required-for-nerve-regeneration-through-slit2-3-mediated-contact-inhibition-of-locomotion
#8
JOURNAL ARTICLE
Julian J A Hoving, Elizabeth Harford-Wright, Patrick Wingfield-Digby, Anne-Laure Cattin, Mariana Campana, Alex Power, Toby Morgan, Erica Torchiaro, Victor Quereda, Alison C Lloyd
Collective cell migration is fundamental for the development of organisms and in the adult, for tissue regeneration and in pathological conditions such as cancer. Migration as a coherent group requires the maintenance of cell-cell interactions, while contact inhibition of locomotion (CIL), a local repulsive force, can propel the group forward. Here we show that the cell-cell interaction molecule, N-cadherin, regulates both adhesion and repulsion processes during rat Schwann cell (SC) collective migration, which is required for peripheral nerve regeneration...
April 9, 2024: ELife
https://read.qxmd.com/read/38588709/protective-role-of-mertk-in-diabetic-peripheral-neuropathy-via-inhibition-of-the-nf-%C3%AE%C2%BAb-signaling-pathway
#9
JOURNAL ARTICLE
Xiaoyang Su, Wenting Chen, Yidan Fu, Bian Wu, Fugang Mao, Yan Zhao, Qiuping Yang, Danfeng Lan
Diabetic peripheral neuropathy impacts patient quality of life. Increased Mer tyrosine kinase expression has been demonstrated in such patients, yet its mechanism remains unclear. This study established type 2 diabetes mellitus and diabetic peripheral neuropathy models in Sprague Dawley rats via low-dose streptozotocin and a high-fat diet. Mer tyrosine kinase-specific inhibitors were administered by gavage once daily for 2 weeks. Sciatic nerve conduction velocity and nerve structure were measured. The levels of Mer tyrosine kinase, nuclear factor kappa-light-chain-enhancer of activated B cells, tumor necrosis factor-alpha, interleukin-1 beta, and relevant biochemical indexes were detected...
April 8, 2024: Experimental and Clinical Endocrinology & Diabetes
https://read.qxmd.com/read/38588401/decrypting-the-multifaceted-peripheral-neuropathy-based-on-molecular-pathology-and-therapeutics-a-comprehensive-review
#10
REVIEW
Praysha Patel, Krishna Thakkar, Div Shah, Umang Shah, Nilesh Pandey, Jayesh Patel, Alkeshkumar Patel
CONTEXT: Peripheral neuropathy (PN) is a multifaceted complication characterized by nerve damage due to oxidative stress, inflammatory mediators, and dysregulated metabolic processes. Early PN manifests as sensory changes that develop progressively in a "stocking and glove" pattern. METHODS AND MECHANISMS: A thorough review of literature has been done to find the molecular pathology, clinical trials that have been conducted to screen the effects of different drugs, current treatments and novel approaches used in PN therapy...
April 8, 2024: Archives of Physiology and Biochemistry
https://read.qxmd.com/read/38585724/pharmacogenomic-synthetic-lethal-screens-reveal-hidden-vulnerabilities-and-new-therapeutic-approaches-for-treatment-of-nf1-associated-tumors
#11
Kyle B Williams, Alex T Larsson, Bryant J Keller, Katherine E Chaney, Rory L Williams, Minu M Bhunia, Garrett M Draper, Tyler A Jubenville, Sue K Rathe, Christopher L Moertel, Nancy Ratner, David A Largaespada
Neurofibromatosis Type 1 (NF1) is a common cancer predisposition syndrome, caused by heterozygous loss of function mutations in the tumor suppressor gene NF1 . Individuals with NF1 develop benign tumors of the peripheral nervous system (neurofibromas), originating from the Schwann cell linage after somatic loss of the wild type NF1 allele, some of which progress further to malignant peripheral nerve sheath tumors (MPNST). There is only one FDA approved targeted therapy for symptomatic plexiform neurofibromas and none approved for MPNST...
March 25, 2024: bioRxiv
https://read.qxmd.com/read/38584513/gdf5-as-a-rejuvenating-treatment-for-age-related-neuromuscular-failure
#12
JOURNAL ARTICLE
Traoré Massiré, Noviello Chiara, Vergnol Amélie, Gentil Christel, Halliez Marius, Saillard Lucile, Gelin Maxime, Forand Anne, Lemaitre Mégane, Guesmia Zoheir, Cadot Bruno, Caldas Eriky, Marty Benjamin, Mougenot Nathalie, Messéant Julien, Strochlic Laure, Sadoine Jeremy, Slimani Lofti, Jolly Ariane, De la Grange Pierre, Hogrel Jean-Yves, Pietri-Rouxel France, Falcone Sestina
Sarcopenia involves a progressive loss of skeletal muscle force, quality and mass during ageing, which results in increased inability and death; however, no cure has been established thus far. Growth differentiation factor 5 (GDF5) has been described to modulate muscle mass maintenance in various contexts. For our proof of concept, we overexpressed GDF5 by AAV vector injection in Tibialis Anterior (TA) muscle of adult aged (20 months) mice and performed molecular and functional analysis of skeletal muscle. We analysed human Vastus Lateralis muscle biopsies from adult young (21-42 years) and aged (77-80 years) donors, quantifying the molecular markers modified by GDF5 overexpression (OE) in mouse muscle...
April 8, 2024: Brain
https://read.qxmd.com/read/38572924/preparation-of-plcl-ecm-nerve-conduits-by-electrostatic-spinning-technique-and-evaluation-in-vitro-and-in-vivo
#13
JOURNAL ARTICLE
Yizhan Ma, Runze Zhang, Xiaoyan Mao, Xiaoming Li, Ting Li, Fang Liang, Jing He, Lili Wen, Weizuo Wang, Xiao Li, Yanhui Zhang, Honghao Yu, Binhan Lu, Tianhao Yu, Qiang Ao
Objective . Artificial nerve scaffolds composed of polymers have attracted great attention as an alternative for autologous nerve grafts recently. Due to their poor bioactivity, satisfactory nerve repair could not be achieved. To solve this problem, we introduced extracellular matrix (ECM) to optimize the materials. Approach. In this study, the ECM extracted from porcine nerves was mixed with Poly(L-Lactide-co- ϵ -caprolactone) (PLCL), and the innovative PLCL/ECM nerve repair conduits were prepared by electrostatic spinning technology...
April 4, 2024: Journal of Neural Engineering
https://read.qxmd.com/read/38572785/stigmasterol-alleviates-neuropathic-pain-by-reducing-schwann-cell-macrophage-cascade-in-drg-by-modulating-il-34-csf1r
#14
JOURNAL ARTICLE
Waimei Si, Zhenni Chen, Jing Bei, Shiquan Chang, Yachun Zheng, Li Gao, Guoping Zhao, Xin Li, Di Zhang
AIMS: This study aimed to investigate the potential therapeutic applications of stigmasterol for treating neuropathic pain. METHODS: Related mechanisms were investigated by DRG single-cell sequencing analysis and the use of specific inhibitors in cellular experiments. In animal experiments, 32 male Sprague-Dawley rats were randomly divided into the sham operation group, CCI group, ibuprofen group, and stigmasterol group. We performed behavioral tests, ELISA, H&E staining and immunohistochemistry, and western blotting...
April 2024: CNS Neuroscience & Therapeutics
https://read.qxmd.com/read/38572074/emerging-role-of-extracellular-vesicles-and-exogenous-stimuli-in-molecular-mechanisms-of-peripheral-nerve-regeneration
#15
REVIEW
Yara Izhiman, Leyla Esfandiari
Peripheral nerve injuries lead to significant morbidity and adversely affect quality of life. The peripheral nervous system harbors the unique trait of autonomous regeneration; however, achieving successful regeneration remains uncertain. Research continues to augment and expedite successful peripheral nerve recovery, offering promising strategies for promoting peripheral nerve regeneration (PNR). These include leveraging extracellular vesicle (EV) communication and harnessing cellular activation through electrical and mechanical stimulation...
2024: Frontiers in Cellular Neuroscience
https://read.qxmd.com/read/38567289/exploring-an-innovative-decellularization-protocol-for-porcine-nerve-grafts-a-translational-approach-to-peripheral-nerve-repair
#16
JOURNAL ARTICLE
Luisa Muratori, Alessandro Crosio, Giulia Ronchi, Debora Molinaro, Pierluigi Tos, Arianna B Lovati, Stefania Raimondo
INTRODUCTION: Peripheral nerves are frequently affected by lesions caused by traumatic or iatrogenic damages, resulting in loss of motor and sensory function, crucial in orthopedic outcomes and with a significant impact on patients' quality of life. Many strategies have been proposed over years to repair nerve injuries with substance loss, to achieve musculoskeletal reinnervation and functional recovery. Allograft have been tested as an alternative to the gold standard, the autograft technique, but nerves from donors frequently cause immunogenic response...
2024: Frontiers in Neuroanatomy
https://read.qxmd.com/read/38566357/a-gelatin-alginate-double-network-hydrogel-nerve-guidance-conduit-fabricated-by-a-chemical-free-gamma-radiation-for-peripheral-nerve-regeneration
#17
JOURNAL ARTICLE
Junghyun Kim, Junggeon Park, Goeun Choe, Sung In Jeong, Hyung Seok Kim, Jae Young Lee
Nerve guidance conduits (NGCs) have been widely developed using various materials for the functional repair of injured or diseased peripheral nerves. Especially, hydrogels are considered highly suitable for the fabrication of NGCs due to their beneficial tissue-mimicking characteristics (e.g., high water content, softness, and porosity). However, the practical applications of hydrogel-based NGCs are hindered due to their poor mechanical properties and complicated fabrication processes. To bridge this gap, we herein developed a novel double-network (DN) hydrogel using alginate and gelatin by a two-step crosslinking process involving chemical-free gamma irradiation and ionic crosslinking...
April 2, 2024: Advanced Healthcare Materials
https://read.qxmd.com/read/38562812/loss-of-prohibitin-2-in-schwann-cells-dysregulates-key-transcription-factors-controlling-developmental-myelination
#18
Emma R Wilson, Gustavo Della-Flora Nunes, Shichen Shen, Seth Moore, Joseph Gawron, Jessica Maxwell, Umair Syed, Edward Hurley, Meghana Lanka, Jun Qu, Laurent Desaubry, Lawrence Wrabetz, Yannick Poitelon, M Laura Feltri
Schwann cells are critical for the proper development and function of the peripheral nervous system, where they form a mutually beneficial relationship with axons. Past studies have highlighted that a pair of proteins called the prohibitins play major roles in Schwann cell biology. Prohibitins are ubiquitously expressed and versatile proteins. We have previously shown that while prohibitins play a crucial role in Schwann cell mitochondria for long-term myelin maintenance and axon health, they may also be present at the Schwann cell-axon interface during development...
March 20, 2024: bioRxiv
https://read.qxmd.com/read/38561075/dual-layer-conduit-containing-vegf-a-transfected-schwann-cells-promotes-peripheral-nerve-regeneration-via-angiogenesis
#19
JOURNAL ARTICLE
Yuye Huang, Kai Ye, Andong He, Shaobo Wan, Miaoben Wu, Donghao Hu, Kailei Xu, Peng Wei, Jun Yin
Peripheral nerve injuries (PNIs) can cause neuropathies and significantly affect the patient's quality of life. Autograft transplantation is the gold standard for conventional treatment; however, its application is limited by nerve unavailability, size mismatch, and local tissue adhesion. Tissue engineering, such as nerve guidance conduits, is an alternative and promising strategy to guide nerve regeneration for peripheral nerve repair; however, only a few conduits could reach the high repair efficiency of autografts...
March 30, 2024: Acta Biomaterialia
https://read.qxmd.com/read/38558569/novel-aav-variants-with-improved-tropism-for-human-schwann-cells
#20
JOURNAL ARTICLE
Matthieu Drouyer, Tak-Ho Chu, Elodie Labit, Florencia Haase, Renina Gale Navarro, Deborah Nazareth, Nicole Rosin, Jessica Merjane, Suzanne Scott, Marti Cabanes-Creus, Adrian Westhaus, Erhua Zhu, Rajiv Midha, Ian E Alexander, Jeff Biernaskie, Samantha L Ginn, Leszek Lisowski
Gene therapies and associated technologies are transforming biomedical research and enabling novel therapeutic options for patients living with debilitating and incurable genetic disorders. The vector system based on recombinant adeno-associated viral vectors (AAVs) has shown great promise in recent clinical trials for genetic diseases of multiple organs, such as the liver and the nervous system. Despite recent successes toward the development of novel bioengineered AAV variants for improved transduction of primary human tissues and cells, vectors that can efficiently transduce human Schwann cells (hSCs) have yet to be identified...
June 13, 2024: Molecular Therapy. Methods & Clinical Development
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