The emerging role of microplastics in systemic toxicity: Involvement of reactive oxygen species (ROS)

The Science of The Total Environment, Год журнала: 2023, Номер 895, С. 165076 - 165076

Опубликована: Июнь 28, 2023

Язык: Английский

---

Thioredoxin (Trx): A redox target and modulator of cellular senescence and aging-related diseases

Redox Biology, Год журнала: 2024, Номер 70, С. 103032 - 103032

Опубликована: Янв. 21, 2024

Thioredoxin (Trx) is a compact redox-regulatory protein that modulates cellular redox state by reducing oxidized proteins. Trx exhibits dual functionality as an antioxidant and cofactor for diverse enzymes transcription factors, thereby exerting influence over their activity function. has emerged pivotal biomarker various diseases, particularly those associated with oxidative stress, inflammation, aging. Recent clinical investigations have underscored the significance of in disease diagnosis, treatment, mechanistic elucidation. Despite its paramount importance, intricate interplay between senescence-a condition characterized irreversible growth arrest induced multiple aging stimuli-remains inadequately understood. In this review, our objective to present comprehensive up-to-date overview structure function Trx, involvement signaling pathways senescence, association age-related well potential therapeutic target. Our review aims elucidate novel extensive role senescence while highlighting implications diseases.

Язык: Английский

---

Male reproductive ageing: a radical road to ruin

Human Reproduction, Год журнала: 2023, Номер 38(10), С. 1861 - 1871

Опубликована: Авг. 10, 2023

In modern post-transition societies, we are reproducing later and living longer. While the impact of age on female reproductive function has been well studied, much less is known about intersection male reproduction. Our current understanding that advancing brings forth a progressive decline in fertility accompanied by reduction circulating testosterone levels appearance age-dependent pathologies including benign prostatic hypertrophy erectile dysfunction. Paternal ageing also associated with profound increase sperm DNA damage, multiple epigenetic changes germ line an elevated mutational load offspring. The net result such disease burden carried progeny males, dominant genetic diseases as Apert syndrome achondroplasia, neuropsychiatric conditions autism spontaneous schizophrenia. basis these age-related effects appears to involve two fundamental mechanisms. first positive selection mechanism whereby stem cells containing mutations mitogen-activated protein kinase pathway gain selective advantage over their non-mutant counterparts exhibit significant clonal expansion passage time. second dependent oxidative stress which impairs steroidogenic capacity Leydig cells, disrupts ability Sertoli support normal differentiation functional integrity spermatozoa. Given central importance defining chronological reproduction, there may be role for antioxidants clinical management this process. animal studies supportive strategy, carefully designed trials now needed if realize therapeutic potential approach context.

Язык: Английский

---

Impact of NQO1 dysregulation in CNS disorders

Journal of Translational Medicine, Год журнала: 2024, Номер 22(1)

Опубликована: Янв. 2, 2024

NAD(P)H Quinone Dehydrogenase 1 (NQO1) plays a pivotal role in the regulation of neuronal function and synaptic plasticity, cellular adaptation to oxidative stress, neuroinflammatory degenerative processes, tumorigenesis central nervous system (CNS). Impairment NQO1 activity CNS can result abnormal neurotransmitter release clearance, increased aggravated injury/death. Furthermore, it cause disturbances neural circuit neurotransmission. The abnormalities enzyme have been linked pathophysiological mechanisms multiple neurological disorders, including Parkinson's disease, Alzheimer's epilepsy, sclerosis, cerebrovascular traumatic brain injury, malignancy. contributes various dimensions treatment response tumors. precise through which contribute these disorders continue be subject ongoing research. Building upon existing knowledge, present study reviews current investigations describing dysregulations disorders. This emphasizes potential as biomarker diagnostic prognostic approaches, well its suitability target for drug development strategies

Язык: Английский

---

Molecular hallmarks of ageing in amyotrophic lateral sclerosis

Cellular and Molecular Life Sciences, Год журнала: 2024, Номер 81(1)

Опубликована: Март 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.

Язык: Английский

---

Role of Oxidative Stress in Blood–Brain Barrier Disruption and Neurodegenerative Diseases

Antioxidants, Год журнала: 2024, Номер 13(12), С. 1462 - 1462

Опубликована: Ноя. 28, 2024

Upregulation of reactive oxygen species (ROS) levels is a principal feature observed in the brains neurodegenerative diseases such as Parkinson’s disease (PD) and Alzheimer’s (AD). In these diseases, oxidative stress can disrupt blood–brain barrier (BBB). This disruption allows neurotoxic plasma components, blood cells, pathogens to enter brain, leading increased ROS production, mitochondrial dysfunction, inflammation. Collectively, factors result protein modification, lipid peroxidation, DNA damage, and, ultimately, neural cell damage. this review article, we present mechanisms by which damage leads BBB breakdown brain diseases. Additionally, summarize potential therapeutic approaches aimed at reducing that contributes

Язык: Английский

---

OSP-1 protects neurons from autophagic cell death induced by acute oxidative stress

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Янв. 2, 2025

Oxidative stress, caused by the accumulation of reactive oxygen species (ROS), is a pathological factor in several incurable neurodegenerative conditions as well stroke. However, our knowledge genetic elements that can be manipulated to protect neurons from oxidative stress-induced cell death still very limited. Here, using Caenorhabditis elegans model system, combined with optogenetic tool KillerRed spatially and temporally control ROS generation, we identify previously uncharacterized gene, stress protective 1 (osp-1), protects C. damage. Using rodent human cultures, also show effect OSP-1 extends mammalian cells. Moreover, demonstrate functions strictly cell-autonomous fashion, it localizes endoplasmic reticulum (ER) where has an ER-remodeling function. Finally, present evidence suggesting may exert its neuroprotective function influencing autophagy. Our results point potential role modulating autophagy, suggest overactivation this cellular process could contribute neuronal triggered How impacts poorly understood. Here authors reveal autophagy following contributes discover process.

Язык: Английский

---

The Reduction in the Mitochondrial Membrane Potential in Aging: The Role of the Mitochondrial Permeability Transition Pore

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(15), С. 12295 - 12295

Опубликована: Авг. 1, 2023

It is widely reported that the mitochondrial membrane potential, ∆Ψm, reduced in aging animals. was recently suggested lower ∆Ψm aged animals modulates bioenergetics and this effect a major cause of since artificially increased C. elegans lifespan. Here, I critically review studies reduction animals, including worms, conclude many these observations are best interpreted as evidence fraction depolarized mitochondria cells because enhanced activation permeability transition pore, mPTP. Activation voltage-gated mPTP depolarizes mitochondria, inhibits oxidative phosphorylation, releases large amounts calcium mROS, depletes cellular NAD+, thus accelerating degenerative diseases aging. Since inhibition shown to restore retard aging, lifespan extension by generated explained Similarly, unfolded protein response preservation dietary restriction treatment resulting from or mPTP, respectively.

Язык: Английский

---

Physical Exercise-Induced Activation of NRF2 and BDNF as a Promising Strategy for Ferroptosis Regulation in Parkinson’s Disease

Neurochemical Research, Год журнала: 2024, Номер 49(7), С. 1643 - 1654

Опубликована: Май 24, 2024

Язык: Английский

---

A Nanozyme-Boosted MOF-CRISPR Platform for Treatment of Alzheimer’s Disease

Nano Letters, Год журнала: 2024, Номер 24(32), С. 9906 - 9915

Опубликована: Авг. 1, 2024

Rectifying the aberrant microenvironment of a disease through maintenance redox homeostasis has emerged as promising perspective with significant therapeutic potential for Alzheimer's (AD). Herein, we design and construct novel nanozyme-boosted MOF-CRISPR platform (CMOPKP), which can maintain rescue impaired AD. By modifying targeted peptides KLVFFAED, CMOPKP traverse blood–brain barrier deliver CRISPR activation system precise Nrf2 signaling pathway downstream proteins in regions characterized by oxidative stress, thereby reinstating neuronal antioxidant capacity preserving homeostasis. Furthermore, cerium dioxide possessing catalase enzyme-like activity synergistically alleviate stress. Further vivo studies demonstrate that effectively cognitive impairment 3xTg-AD mouse models. Therefore, our presents an effective way regulating AD, shows promise strategy mitigating stress

Язык: Английский

---