SMN Deficiency Induces an Early Non-Atrophic Myopathy with Alterations in the Contractile and Excitatory Coupling Machinery of Skeletal Myofibers in the SMN∆7 Mouse Model of Spinal Muscular Atrophy DOI Open Access
Marı́a T. Berciano,

Alaó Gatius,

Alba Puente-Bedia

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(22), P. 12415 - 12415

Published: Nov. 19, 2024

Spinal muscular atrophy (SMA) is caused by a deficiency of the ubiquitously expressed survival motor neuron (SMN) protein. The main pathological hallmark SMA degeneration lower neurons (MNs) with subsequent denervation and skeletal muscle. However, increasing evidence indicates that low SMN levels not only are detrimental to central nervous system (CNS) but also directly affect other peripheral tissues organs, including To better understand potential primary impact in muscle, we explored cellular, ultrastructural, molecular basis myopathy SMNΔ7 mouse model severe at an early postnatal period (P0-7) prior muscle MN loss (preneurodegenerative [PND] stage). This contrasts neurodegenerative (ND) stage (P8-14), which occur. At PND stage, found SMN∆7 mice displayed signs dysfunction overt myofiber alterations absence atrophy. We provide essential new ultrastructural data on focal segmental lesions myofibrillar contractile apparatus. These were observed association specific myonuclear domains included abnormal accumulations actin-thin myofilaments, sarcomere disruption, formation minisarcomeres. sarcoplasmic reticulum triads exhibited alterations, suggesting decoupling during excitation-contraction process. Finally, changes intermyofibrillar mitochondrial organization dynamics, indicative biogenesis overactivation, found. Overall, our results demonstrated induces loss-independent myofibers essentially contribute myopathy. strongly supports growing body indicating existence intrinsic further reinforces relevance this tissue as key therapeutic target for disease.

Language: Английский

New insights into the role of mitochondrial dynamics in oxidative stress-induced diseases DOI Open Access
Sisi Chen, Qilong Li,

Hanjing Shi

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 178, P. 117084 - 117084

Published: Aug. 1, 2024

The accumulation of excess reactive oxygen species (ROS) can lead to oxidative stress (OS), which induce gene mutations, protein denaturation, and lipid peroxidation directly or indirectly. expression is reduced ATP level in cells, increased cytoplasmic Ca

Language: Английский

Citations

37
Thymoquinone-Loaded Chitosan Nanoparticles Combat Testicular Aging and Oxidative Stress Through SIRT1/FOXO3a Activation: An In Vivo and In Vitro Study DOI Creative Commons

Enas A. Kasem,

Ghaith M. Hamza, Nagi M. El‐Shafai

et al.

Pharmaceutics, Journal Year: 2025, Volume and Issue: 17(2), P. 210 - 210

Published: Feb. 6, 2025

Background: Aging is a complex biological process characterized by the accumulation of molecular and cellular damage over time, often driven oxidative stress. This stress particularly detrimental to testes, where it causes degeneration, reduced testosterone levels, compromised fertility. D-galactose (D-gal) commonly used model aging as induces stress, mimicking age-related damage. Testicular significant concern due its implications for reproductive health hormonal balance. research examines protection thymoquinone (TQ) or thymoquinone-loaded chitosan nanoparticles (NCPs) against (D-gal)-induced in rat focusing on biochemical, histological, changes. Aging, which largely leads testicular reducing D-gal widely ability induce mimic TQ, bioactive ingredient Nigella sativa, has earned reputation anti-inflammatory, anti-apoptotic, antioxidant characteristics, but therapeutic application limited poor bioavailability. Methods: Thymoquinone was loaded into enhance efficacy, this hypothesized improve stability Four groups male Wistar rats participated study: one control, D-gal, + last NCP. Results: The results exhibited that substantially increased injury, caused Treatment with TQ NCPs significantly improved enzyme restored showing stronger protective effect than alone. A histological analysis confirmed better preserved structure function. Additionally, NCP treatment upregulated expression key genes resistance, mitochondrial function, health, including SIRT1, FOXO3a, TERT. Conclusions: findings suggest offer enhanced aging-related compared alone, likely bioavailability provided nanoparticle delivery system. emphasizes potential more effective strategy mitigating dysfunction. Future should further explore mechanisms underlying these effects.

Language: Английский

Citations

1
Pharmacological approaches to enhance mitochondrial biogenesis: focus on PGC-1Α, AMPK, and SIRT1 in cellular health DOI

Ahmet Alperen Palabiyik,

Esra Palabıyık

Molecular Biology Reports, Journal Year: 2025, Volume and Issue: 52(1)

Published: Feb. 28, 2025

Language: Английский

Citations

1
NTRK1 knockdown induces mouse cognitive impairment and hippocampal neuronal damage through mitophagy suppression via inactivating the AMPK/ULK1/FUNDC1 pathway DOI Creative Commons
Kai Yang, Jue Wu, Shang Li

et al.

Cell Death Discovery, Journal Year: 2023, Volume and Issue: 9(1)

Published: Oct. 31, 2023

Abstract Hippocampal neuronal damage may induce cognitive impairment. Neurotrophic tyrosine kinase receptor 1 (NTRK1) reportedly regulates damage, although the underlying mechanism remains unclear. The present study aimed to investigate role of NTRK1 in mouse hippocampal and specific mechanism. A NTRK1-knockdown model was established subjected pre-treatment with BAY-3827, followed by a behavioral test, Nissl staining, NeuN immunofluorescence (IF) staining evaluate impairment damage. Next, an vitro analysis conducted using CCK-8 assay, TUNEL IF DCFH-DA JC-1 ATP content mRFP-eGFP-LC3 LC3-II elucidate effect on activity, apoptosis, mitochondrial function, autophagy. Subsequently, rescue experiments were performed subjecting neurons O304 Rapamycin. AMPK/ULK1/FUNDC1 pathway activity mitophagy detected western blotting (WB) analysis. Resultantly, vivo revealed that knockdown induced tissue addition inactivating tissues mice. treatment BAY-3827 exacerbated depressive-like behavior knockdown. results indicated attenuated viability, expression, production, membrane potential, mitophagy, while enhancing apoptosis ROS production neurons. Conversely, rapamycin abrogated suppression promotion upon silencing. Conclusively, induces through via pathway. This finding would provide insight leading development novel strategies for due

Language: Английский

Citations

18
Mitochondrial targeted antioxidants as potential therapy for huntington’s disease DOI
Shubham Upadhayay, Puneet Kumar

Pharmacological Reports, Journal Year: 2024, Volume and Issue: 76(4), P. 693 - 713

Published: July 9, 2024

Language: Английский

Citations

5
Manganese-based nanozymes as broad-spectrum antioxidants against cisplatin-induced skeletal muscle atrophy DOI
Wenbo Niu, Zhenjun Chen, Fujing Wang

et al.

Chemical Engineering Journal, Journal Year: 2025, Volume and Issue: unknown, P. 159213 - 159213

Published: Jan. 1, 2025

Language: Английский

Citations

0
CHOP‐Mediated Disruption of Hippocampal Synaptic Plasticity and Neuronal Activity Contributes to Chronic Pain‐Related Cognitive Deficits DOI Creative Commons

Qingsheng Meng,

Songxue Su,

Lei Lei

et al.

CNS Neuroscience & Therapeutics, Journal Year: 2025, Volume and Issue: 31(1)

Published: Jan. 1, 2025

ABSTRACT Objectives Endoplasmic reticulum (ER) stress‐induced protein homeostasis perturbation is a core pathological element in the pathogenesis of neurodegenerative diseases. This study aims to clarify unique role played by C/EBP homologous (CHOP) as biomarker unfolded response (UPR) etiology chronic pain and related cognitive impairments following constrictive nerve injury (CCI). Methods The memory capability CCI was assessed utilizing Morris water maze (MWM) fear conditioning test (FCT). Activation UPR quantified assessing levels CHOP key ER stress sensors. terminal deoxynucleotidyl transferase (TdT) dUTP nick‐end labeling (TUNEL) assay cleaved caspase‐3 were utilized assess apoptosis level. Synaptic plasticity via modified Golgi‐Cox staining method, long‐term potentiation (LTP) measurements taken. Neuronal activity determined immunofluorescence fiber photometry. Knockdown alleviation selectively induced LV‐Ddit3‐shRNAs chemical chaperone 4‐phenylbutyric acid (4‐PBA), respectively. Results Mice subjected displayed enduring evident on Days 21–28 post‐surgery. Following CCI, changes dorsal CA1 (dCA1) manifested dilation, upregulation upstream signaling molecules, reduced dendritic spine density, PSD95 levels, impaired LTP. Additionally, co‐localization CaMKIIα/c‐Fos CaMKIIα dCA1 ‐mediated calcium significantly reduced, while activation found mitigate mice. Selective knockdown enhanced synaptic neuron activity, 4‐PBA treatment alleviated stress, synergistically improving deficits associated with pain. Conclusion CCI‐induced impairs neuronal leading pain‐related deficits.

Language: Английский

Citations

0
Beneficial Effects of the Herbal Medicine Zuo Gui Wan in a Mice Model of Alzheimer's Disease via Drp1-Mediated Inhibition of Mitochondrial Fission and Activation of AMPK/PGC-1α-regulated Mitochondrial Bioenergetics DOI

Xirui Yan,

Yifang Yang, Weilin Huang

et al.

Journal of Ethnopharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 119425 - 119425

Published: Jan. 1, 2025

Language: Английский

Citations

0
Exome sequencing identifies novel genes associated with cerebellar volume and microstructure DOI Creative Commons
Yuanyuan Liang,

Dongrui Ma,

Mengjie Li

et al.

Communications Biology, Journal Year: 2025, Volume and Issue: 8(1)

Published: March 1, 2025

Proteins encoded by exons are critical for cellular functions, and mutations in these genes often result significant phenotypic effects. The cerebellum is linked to various heritable human disease phenotypes, yet genome-wide association studies have struggled capture the effects of rare variants on cerebellar traits. This study conducts a large-scale exome analysis using data from approximately 35,000 UK Biobank participants, examining seven traits, including total volume white matter microstructure. We identify 90 associated with 60 which were previously unreported studies. Notable findings include discovery like PRKRA TTK, as well RASGRP3, Gene enrichment reveals associations non-coding RNA processing, cognitive function, neurodegenerative diseases, mental disorders, suggesting shared biological mechanisms between phenotypes neuropsychiatric diseases. Large-scale UKBB identifies genes, novel, suggests links microstructure,

Language: Английский

Citations

0
ApoE4 dysregulation incites depressive symptoms and mitochondrial impairments in mice DOI Creative Commons
Weifen Li, Tahir Ali, Kaiwu He

et al.

Journal of Cellular and Molecular Medicine, Journal Year: 2024, Volume and Issue: 28(7)

Published: March 20, 2024

Apolipoprotein E4 (ApoE4) is involved in the stress-response processes and hypothesized to be a risk factor for depression by means of mitochondrial dysfunction. However, their exact roles underlying mechanisms are largely unknown. ApoE4 transgenic mice (B6. Cg-ApoEtm1Unc Cdh18Tg( GFAP-APOE i4)1Hol /J) were subjected stress (lipopolysaccharides, LPS) elucidate aetiology ApoE4-induced depression. LPS treatment significantly aggravated depression-like behaviours, concurrent with neuroinflammation impaired changes, melatonin/Urolithin A (UA) + 5-aminoimidazole-4-carboxamide 1-β-D-ribofuranoside (AICAR) reversed these effects mice. Concurrently, exhibited mitophagy deficits, which could further exacerbated stimulation, as demonstrated reduced Atg5, Beclin-1 Parkin levels, while PINK1 levels increased. changes melatonin treatment. Additionally, proteomic profiling suggested mitochondria-related signalling network mice, may underlie exaggerated response LPS. Furthermore, HEK 293T cells transfected showed mitochondria-associated protein defects, including PGC-1α, TFAM, p-AMPKα, LC3B impairments. it aggravates impairment (particularly mitophagy), can attenuated triggering autophagy. Collectively, dysregulation enhanced depressive behaviour upon stimulation.

Language: Английский

Citations

4