Therapeutic Targeting of the GSK3β-CUGBP1 Pathway in Myotonic Dystrophy DOI Open Access
Maggie Lutz,

Miranda Levanti,

Rebekah Karns

и другие.

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(13), С. 10650 - 10650

Опубликована: Июнь 26, 2023

Myotonic Dystrophy type 1 (DM1) is a neuromuscular disease associated with toxic RNA containing expanded CUG repeats. The developing therapeutic approaches to DM1 target mutant or correct early events downstream of the RNA. We have previously described benefits correction GSK3β-CUGBP1 pathway in mice (HSALR model) expressing 250 repeats using GSK3 inhibitor tideglusib (TG). Here, we show that TG treatments corrected expression ~17% genes misregulated mice, including involved cell transport, development and differentiation. chloride channel (Clcn1), key trigger myotonia DM1, was also by TG. found long (DMSXL beneficial not only at prenatal postnatal stages, but during adulthood. Using mouse model dysregulated CUGBP1, which mimics alterations showed CUGBP1 contributes toxicity changing gene causing CNS abnormalities. These data critical role muscle pathologies, suggesting inhibitors patients different forms DM1.

Язык: Английский

Oxidative stress: Roles in skeletal muscle atrophy DOI
Han Zhang,

Guangdong Qi,

Kexin Wang

и другие.

Biochemical Pharmacology, Год журнала: 2023, Номер 214, С. 115664 - 115664

Опубликована: Июнь 16, 2023

Язык: Английский

Процитировано

104

Ginkgolide B increases healthspan and lifespan of female mice DOI
Chien‐Wei Lee,

Belle Yu‐Hsuan Wang,

Sharon H.A. Wong

и другие.

Nature Aging, Год журнала: 2025, Номер unknown

Опубликована: Янв. 31, 2025

Язык: Английский

Процитировано

4

Endoplasmic reticulum stress and unfolded protein response: Roles in skeletal muscle atrophy DOI
Yanan Ji, Quan Jiang,

Bingqian Chen

и другие.

Biochemical Pharmacology, Год журнала: 2025, Номер 234, С. 116799 - 116799

Опубликована: Фев. 12, 2025

Язык: Английский

Процитировано

4

Chronic kidney disease-induced muscle atrophy: Molecular mechanisms and promising therapies DOI Creative Commons
Kexin Wang,

Liu Qing-yuan,

Mingyu Tang

и другие.

Biochemical Pharmacology, Год журнала: 2022, Номер 208, С. 115407 - 115407

Опубликована: Дек. 31, 2022

Chronic kidney disease (CKD) is a high-risk chronic catabolic due to its high morbidity and mortality. CKD accompanied by many complications, leading poor quality of life, serious complications may even threaten the life patients. Muscle atrophy common complication CKD. sarcopenia in patients have complex pathways that are related multiple mechanisms factors. This review not only discusses which inflammation, oxidative stress, mitochondrial dysfunction promote CKD-induced muscle but also explores other CKD-related such as metabolic acidosis, vitamin D deficiency, anorexia, excess angiotensin II, well factors play role atrophy, insulin resistance, hormones, hemodialysis, uremic toxins, intestinal flora imbalance, miRNA. We highlight potential treatments drugs can effectively treat terms treatment, nutritional supplementation, physical exercise, drug intervention, thereby helping improve prognosis

Язык: Английский

Процитировано

52

Opposing gene regulatory programs governing myofiber development and maturation revealed at single nucleus resolution DOI Creative Commons
Matthieu Dos Santos, Akansha M. Shah, Yichi Zhang

и другие.

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Июль 19, 2023

Abstract Skeletal muscle fibers express distinct gene programs during development and maturation, but the underlying regulatory networks that confer stage-specific myofiber properties remain unknown. To decipher these distinctive how they respond to neural activity, we generated a combined multi-omic single-nucleus RNA-seq ATAC-seq atlas of mouse skeletal at multiple stages embryonic, fetal, postnatal life. We found Myogenin, Klf5, Tead4 form transcriptional complex synergistically activates expression genes in developing myofibers. During transcription factor Maf acts as switch activate mature fast program. In muscles mutant mice lacking voltage-gated L-type Ca 2+ channels (Cav1.1), maturation are impaired. These findings provide reveal genetic links between formation, contraction.

Язык: Английский

Процитировано

27

Denervation alters the secretome of myofibers and thereby affects muscle stem cell lineage progression and functionality DOI Creative Commons
Henriette Henze, Sören S. Hüttner, Philipp Koch

и другие.

npj Regenerative Medicine, Год журнала: 2024, Номер 9(1)

Опубликована: Март 1, 2024

Skeletal muscle function crucially depends on innervation while repair of skeletal relies resident stem cells (MuSCs). However, it is poorly understood how affects MuSC properties and thereby regeneration muscle. Here, we report that loss causes precocious activation MuSCs concomitant with the expression markers myogenic differentiation. This aberrant after accompanied by profound alterations mRNA protein level. Combination injury results in impaired including shifts populations delayed maturation regenerating myofibers. We further demonstrate leads to myofibers their secretome, which then affect behavior. In particular, identify an increased secretion Osteopontin transforming growth factor beta 1 (Tgfb1) isolated from mice had undergone sciatic nerve transection. The altered secretome upregulation early activating transcription factors, such as Junb, target genes MuSCs. combination different secreted factors required cause observed innervation. These data first causing underscoring importance proper for functionality

Язык: Английский

Процитировано

11

The success of biomaterial-based tissue engineering strategies for peripheral nerve regeneration DOI Creative Commons
Yuhui Jiang,

Xiaoxuan Tang,

Tao Li

и другие.

Frontiers in Bioengineering and Biotechnology, Год журнала: 2022, Номер 10

Опубликована: Окт. 18, 2022

Peripheral nerve injury is a clinically common that causes sensory dysfunction and locomotor system degeneration, which seriously affects the quality of patients’ daily life. Long gapped defects in large are difficult to repair via surgery limited donor source autologous greatly challenges successful by transplantation. Significantly, remarkable progress has been made repairing peripheral using artificial grafts variety products for have emerged approved globally recent years. The raw materials these commercial includes natural/synthetic polymers, extracellular matrix. Despite lot effort, desirable functional recovery still remains great long defects. Thus this review discusses development tissue engineering design bionic improving local microenvironment accelerating regeneration against disorder, may provide potential strategies gaps or thick multifunctional biomaterials.

Язык: Английский

Процитировано

17

Neuromuscular Dysfunction Precedes Cognitive Impairment in a Mouse Model of Alzheimer’s Disease DOI Creative Commons
Matthew H. Brisendine, Anna S. Nichenko, Aloka B. Bandara

и другие.

Function, Год журнала: 2023, Номер 5(1)

Опубликована: Ноя. 23, 2023

Abstract Alzheimer’s disease (AD) develops along a continuum that spans years prior to diagnosis. Decreased muscle function and mitochondrial respiration occur earlier in those develop AD; however, it is unknown what causes these peripheral phenotypes of the brain. Exercise promotes muscle, mitochondria, cognitive health proposed be potential therapeutic for AD, but no study has investigated how skeletal adapts exercise training an AD-like context. Utilizing 5xFAD mice, AD model ad-like pathology impairments around 6 mo age, we examined vivo neuromuscular adapations (mitochondrial RNA sequencing) before manifestation overt impairment. We found mice dysfunction beginning as early 4 characterized by impaired nerve-stimulated torque production compound nerve action sciatic nerve. Furthermore, had altered, sex-dependent, adaptive responses gene expression) absence Changes systems, specifically neural communication may harbingers have implications lifestyle interventions, like exercise, AD.

Язык: Английский

Процитировано

10

Janus kinase inhibitors are potential therapeutics for amyotrophic lateral sclerosis DOI Creative Commons
Peter J. Richardson, Daniel P. Smith,

Alex de Giorgio

и другие.

Translational Neurodegeneration, Год журнала: 2023, Номер 12(1)

Опубликована: Окт. 12, 2023

Amyotrophic lateral sclerosis (ALS) is a poorly treated multifactorial neurodegenerative disease associated with multiple cell types and subcellular organelles. As other diseases, it likely that drugs will need to target processes be effective. We review here the role of Janus kinase (JAK)/Signal transducer activator transcription (STAT) signalling in ALS, confirm association this fundamental ALS using BenevolentAI Knowledge Graph, demonstrate inhibitors pathway could reduce pathophysiology neurons, glia, muscle fibres, blood cells. Specifically, we suggest inhibition JAK enzymes by approved known as Jakinibs STAT3 activation modify progress disease. Analysis highlights baricitinib suitable candidate due its ability penetrate central nervous system exert beneficial effects on immune system. Therefore, recommend drug tested appropriately designed clinical trials for ALS.

Язык: Английский

Процитировано

9

Treatment of Denervated Muscle Atrophy by Injectable Dual‐Responsive Hydrogels Loaded with Extracellular Vesicles DOI Creative Commons
Ziheng Bu, Jianxing Jing, Wei Liu

и другие.

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Янв. 21, 2025

Abstract Denervated muscle atrophy, a common outcome of nerve injury, often results in irreversible fibrosis due to the limited effectiveness current therapeutic interventions. While extracellular vesicles (EVs) offer promise for treating their potential is hindered by challenges delivery and bioactivity within complex microenvironment injury site. To address this issue, an injectable hydrogel developed that responsive both ultrasound pH, with inherent anti‐inflammatory antioxidant properties, designed improve targeted stem cell‐derived EVs. This system allows controlled release EVs from human umbilical cord mesenchymal cells (HUC‐MSCs), adapting specific conditions environment. In vivo studies using rat model demonstrated EV‐loaded (EVs@UR‐gel) significantly preserved function. Six weeks post‐nerve reconstruction, treated rats exhibited strength, circumference, wet weight reaching 89.53 ± 0.96%, 76.02 7.49%, 88.0 2.65% healthy controls, respectively, alongside improvement sciatic index (−0.11±0.09). platform presents novel approach maintaining EV bioactivity, enabling tunable based on disease state, facilitating restoration structure

Язык: Английский

Процитировано

0