Neurochemical Journal, Journal Year: 2024, Volume and Issue: 18(3), P. 406 - 414
Published: Sept. 1, 2024
Language: Английский
Advanced Science, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 21, 2025
Diabetic foot ulcer (DFU) is a common and severe complication of diabetes mellitus, the etiology which remains insufficiently understood, particularly regarding involvement extracellular vesicles (EVs). In this study, nanoflow cytometry to detect EVs in DFU skin tissues used found significant increase Translocase Outer Mitochondrial Membrane 20 (TOM20)+ mitochondrial-derived (MDVs). The role MDVs yet be reported. Using single-cell datasets, it discovered that may regulated by Sorting Nexin 9 (SNX9). vitro experiments revealed secreted fibroblasts cultured high glucose medium exhibited similar composition protein enrichment results those tissues, suggesting their potential as an ideal surrogate. These promoted apoptosis intracellular oxidative stress, disrupted mitochondrial structure, reduced aerobic metabolism target cells. vivo also showed MDV drops hindered wound healing diabetic mice; however, effect rescued SNX9 inhibitors, restoring dynamics balance. Under conditions, significantly upregulated stress levels induced dysfunction. This study proposes targeting therapeutic strategy for DFU.
Language: Английский
Citations
4
Cellular and Molecular Life Sciences, Journal Year: 2024, Volume and Issue: 81(1)
Published: March 2, 2024
Abstract Amyotrophic lateral sclerosis (ALS) is a fatal, severely debilitating and rapidly progressing disorder affecting motor neurons in the brain, brainstem, spinal cord. Unfortunately, there are few effective treatments, thus remains critical need to find novel interventions that can mitigate against its effects. Whilst aetiology of ALS unclear, ageing major risk factor. Ageing slowly progressive process marked by functional decline an organism over lifespan. However, it unclear how promotes ALS. At molecular cellular level specific hallmarks characteristic normal ageing. These highly inter-related overlap significantly with each other. Moreover, whilst process, striking similarities at between these factors neurodegeneration Nine were originally proposed: genomic instability, loss telomeres, senescence, epigenetic modifications, dysregulated nutrient sensing, proteostasis, mitochondrial dysfunction, stem cell exhaustion, altered inter-cellular communication. recently (2023) expanded include dysregulation autophagy, inflammation dysbiosis. Hence, given latest updates hallmarks, their close association disease processes ALS, new examination relationship pathophysiology warranted. In this review, we describe possible mechanisms which impacts on neurodegenerative implicated therapeutic may arise from this.
Language: Английский
Citations
13
Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 102, P. 102545 - 102545
Published: Oct. 17, 2024
Language: Английский
Citations
12
Experimental Gerontology, Journal Year: 2024, Volume and Issue: 190, P. 112428 - 112428
Published: April 11, 2024
Mitochondrial dysregulation in skeletal myocytes is considered a major factor aged sarcopenia. In this study, we aimed to study the effects of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) on Sestrin2-mediated mechanistic target rapamycin complex 1 (mTORC1) muscles.
Language: Английский
Citations
4
Neuropharmacology, Journal Year: 2024, Volume and Issue: 261, P. 110153 - 110153
Published: Sept. 6, 2024
Language: Английский
Citations
4
Frontiers in Aging Neuroscience, Journal Year: 2025, Volume and Issue: 17
Published: Feb. 7, 2025
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the loss of motor neurons (MNs). Genetic mutations in Optineurin (OPTN) and Superoxide Dismutase 1 (SOD1) have been identified as causal factors for ALS. OPTN immunopositive inclusions confirmed cases ALS with SOD1 mutations. However, role gene caused ambiguous. The murine Optn lentivirus empty vector were injected into G93A mice after discovering variations expression over time. phenotype onset date, life span, locomotor activity, pathological changes spinal cord determined recorded subsequently. In addition, influences on cellular apoptosis, mitochondrial dynamics, mitophagy, neuroinflammation further investigated. was increased at pre-symptomatic phase, but decreased onset. overexpression led to 9.7% delay improved performance mice. also ameliorated MNs 46.8%. Moreover, all these ameliorating effects induced might be due inhibition improvement quality, regulation promotion anti-inflammatory properties. Our data demonstrate that protects MNs, inhibites improves quality regulates neuroinflamation stage.
Language: Английский
Citations
0
Neurobiology of Disease, Journal Year: 2025, Volume and Issue: unknown, P. 106862 - 106862
Published: March 1, 2025
Mitochondria play a central role in essential cellular processes, including energy metabolism, biosynthesis of metabolic substances, calcium ion storage, and regulation cell death. Maintaining mitochondrial quality control is critical for preserving health ensuring function. Given their high demands, neurons depend on effective to sustain functionality. Neuronal senescence, characterized by progressive decline structural integrity function, hallmark neurodegenerative diseases. In senescent neurons, abnormal morphology, functional impairments, increased reactive oxygen species production disrupted mechanisms are frequently observed. Understanding the pathological changes neuronal structure, exploring intricate relationship between health, leveraging interventions provide promising foundation addressing age-related This review highlights key control, biogenesis, dynamics, ubiquitin-proteasome system, autophagy pathways, mitochondria-derived vesicles, inter-organelle communication, while discussing roles senescence potential therapeutic strategies. These insights may pave way innovative treatments mitigate disorders.
Language: Английский
Citations
0
Biology, Journal Year: 2025, Volume and Issue: 14(3), P. 272 - 272
Published: March 7, 2025
Neural excitatory/inhibitory (E/I) imbalance plays a pivotal role in the aging process. However, despite its significant impact, of E/I motor dysfunction and neurodegenerative diseases has not received sufficient attention. This review explores mechanisms underlying through lens balance, emphasizing genetic molecular factors that contribute to this (such as SCN2A, CACNA1C, GABRB3, GRIN2A, SYT, BDNF…). Key regulatory genes, including REST, vps-34, STXBP1, are examined for their roles modulating synaptic activity neuronal function during aging. With insights drawn from ALS, we discuss how disruptions balance pathophysiology age-related dysfunction. The genes discussed above exhibit certain association with neuron (like ALS), relationship had been previously recognized. Innovative therapies, such gene editing technology optogenetic manipulation, emerging promising tools restoring offering hope ameliorating deficits potential these technologies intervene aging-related diseases, challenges direct application human conditions.
Language: Английский
Citations
0
Brain and Behavior, Journal Year: 2025, Volume and Issue: 15(5)
Published: May 1, 2025
ABSTRACT Objective This longitudinal study investigated pathological brain aging in amyotrophic lateral sclerosis (ALS) by evaluating disparities between chronological age and deep learning‐derived structure (BSA) exploring associations with cognitive functional decline. Methods Ten limb‐onset ALS patients (seven males) 10 demographically matched healthy controls (HCs) underwent structural magnetic resonance imaging (sMRI) assessments at baseline follow‐up. The BSA was estimated using the validated volBrain platform. Cognitive domains (language, verbal fluency, executive function, memory, visuospatial skills) global cognition (Persian adaptive Edinburgh Behavioral Screen [ECAS] total score) were assessed along status (ALSFRS‐R). Results exhibited significant BSA‐chronological (Δ = +7.31 years, p 0.009) follow‐up +8.39 0.003), accelerated progression over time ( 0.004). HCs showed no such 0.931). Longitudinal increases correlated function decline r −0.651, 0.042). Higher education predicted preserved language 0.831, 0.003) fluency 0.738, 0.015). ALSFRS‐R paralleled 0.642, 0.045) deterioration 0.667, 0.035). Conclusions is characterized that progresses independently of dysfunction. Education may mitigate decline, while motor aligns impairments. has emerged as a potential biomarker for tracking trajectories ALS, warranting validation larger cohorts.
Language: Английский
Citations
0
Extracellular Vesicles and Circulating Nucleic Acids, Journal Year: 2024, Volume and Issue: 5(2), P. 271 - 275
Published: Jan. 1, 2024
Mitochondria dysfunction is increasingly recognized as a critical factor in various pathogenic processes. The mechanism governing mitochondrial quality control serves an adaptive response, ensuring the preservation of morphology, quantity, and overall function, crucial for cell survival. generation mitochondria-derived vesicles (MDVs) one processes control. Recent literature has suggested MDV heterogeneity; however, detailed characteristics subtypes still need to be studied better. studies have shown that MDVs also play role inter-organelle communication mitochondria besides For instance, Hazan et al. demonstrated functional from Saccharomyces cerevisiae release independent fission machinery. These vesicles, falling within typical size range MDVs, were selectively loaded with proteins, especially ATP synthase subunits. Intriguingly, these maintained membrane potential could generate ATP. Moreover, fuse naïve mitochondria, transferring their Lastly, this study revealed delivery ATP-producing presenting promising avenue rejuvenate ATP-deficient mitochondria. Overall, unveils novel by which maintaining cellular homeostasis important pathological conditions.
Language: Английский
Citations
2