Experimental Neurology, Год журнала: 2025, Номер 386, С. 115174 - 115174
Опубликована: Фев. 2, 2025
Язык: Английский
Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)
Опубликована: Март 1, 2024
Abstract Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) family (PGC-1s), consisting of three members encompassing PGC-1α, PGC-1β, and PGC-1-related coactivator (PRC), was discovered more than a quarter-century ago. PGC-1s are essential coordinators many vital cellular events, including mitochondrial functions, oxidative stress, endoplasmic reticulum homeostasis, inflammation. Accumulating evidence has shown that implicated in diseases, such as cancers, cardiac diseases cardiovascular neurological disorders, kidney motor system metabolic disorders. Examining the upstream modulators co-activated partners identifying critical biological events modulated by downstream effectors contribute to presentation elaborate network PGC-1s. Furthermore, discussing correlation between well summarizing therapy targeting helps make individualized precise intervention methods. In this review, we summarize basic knowledge regarding molecular regulatory network, discuss physio-pathological roles human review application PGC-1s, diagnostic prognostic value several therapies pre-clinical studies, suggest directions for future investigations. This presents immense potential treatment hopefully facilitates promotion new therapeutic targets.
Язык: Английский
Процитировано
83
Neuron, Год журнала: 2023, Номер 111(18), С. 2811 - 2830.e8
Опубликована: Июль 12, 2023
Язык: Английский
Процитировано
52
Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)
Опубликована: Июнь 8, 2024
Abstract Pain is estimated to affect more than 20% of the global population, imposing incalculable health and economic burdens. Effective pain management crucial for individuals suffering from pain. However, current methods assessment treatment fall short clinical needs. Benefiting advances in neuroscience biotechnology, neuronal circuits molecular mechanisms critically involved modulation have been elucidated. These research achievements incited progress identifying new diagnostic therapeutic targets. In this review, we first introduce fundamental knowledge about pain, setting stage subsequent contents. The review next delves into underlying disorders, including gene mutation, epigenetic modification, posttranslational inflammasome, signaling pathways microbiota. To better present a comprehensive view research, two prominent issues, sexual dimorphism comorbidities, are discussed detail based on findings. status quo evaluation manipulation summarized. A series improved innovative strategies, such as therapy, monoclonal antibody, brain-computer interface microbial intervention, making strides towards application. We highlight existing limitations future directions enhancing quality preclinical research. Efforts decipher complexities pathology will be instrumental translating scientific discoveries practice, thereby improving bench bedside.
Язык: Английский
Процитировано
23
International Immunopharmacology, Год журнала: 2023, Номер 116, С. 109793 - 109793
Опубликована: Фев. 1, 2023
Язык: Английский
Процитировано
34
Molecular and Cellular Biochemistry, Год журнала: 2023, Номер 479(6), С. 1513 - 1524
Опубликована: Июль 24, 2023
Abstract Osteoarthritis (OA), a prevalent degenerative joint disease, affects substantial global population. Despite the elusive etiology of OA, recent investigations have implicated mitochondrial dysfunction as significant factor in disease pathogenesis. Mitochondria, pivotal cellular organelles accountable for energy production, exert essential roles metabolism. Hence, can broad-ranging effects on various processes OA development. This comprehensive review aims to provide an overview metabolic alterations occurring and elucidate diverse mechanisms through which contribute These encompass heightened oxidative stress inflammation, perturbed chondrocyte metabolism, compromised autophagy. Furthermore, this will explore potential interventions targeting metabolism means impede or decelerate progression OA. In summary, offers understanding involvement underscores prospective intervention strategies.
Язык: Английский
Процитировано
25
Biochemical Pharmacology, Год журнала: 2024, Номер 228, С. 116182 - 116182
Опубликована: Март 30, 2024
Osteoarthritis (OA) is the most common form of musculoskeletal disease, and its prevalence increasing due to aging population. Chronic pain burdensome symptom OA that significantly lowers patients' quality life, also frequent association with emotional comorbidities, such as anxiety depression. In recent years, both chronic mood alterations have been linked development neuroinflammation in peripheral nervous system, spinal cord supraspinal brain areas. Thus, mechanisms at basis neuroinflammatory process may indicate promising targets for novel treatment affective comorbidities accompany OA. order assess key role maintenance potential involvement psychiatric components, monoiodoacetate (MIA) model rodents has used validated. present commentary article, we aim summarize up-to-date results achieved this experimental OA, focusing on glia activation cytokine production sciatic nerve, dorsal root ganglia (DRGs), The a state anxiety- depression-like behaviors are discussed. Results suggest cells molecules involved represent innovative pharmacological treatments comorbidities.
Язык: Английский
Процитировано
9
Scientific Reports, Год журнала: 2025, Номер 15(1)
Опубликована: Янв. 22, 2025
To investigate the neuroprotective mechanism of mild hypothermia (MH) in ameliorating cerebral ischemia reperfusion (IR) injury. The Pulsinelli's four-vessel ligation method was utilized to establish a rat model global IR role S100A8 MH treatment injury, hippocampus-specific loss or gain function achieved using an adeno-associated virus system. We examined effect over-expression knock-down on SH-SY5Y cell line subjected oxygen-glucose deprivation reoxygenation (OGDR) injury under and delved into underlying mechanisms. significantly ameliorates IR-induced neurological brain. Similarly MH, reduced neuronal oxidative stress, attenuated mitochondrial damage, inhibited apoptosis, improved cognitive rats. Conversely, MH's protective aggravated brain In vitro, low expression decline membrane potential induced by OGDR, stress response, decreased acting as agent nearly equivalent cells. However, these effects MH. Mechanistically, down-regulated expression, enhancing via activation CAMKK2/AMPK signaling pathway. Moreover, with treatment, administration CAMKK2 AMPK inhibitors STO-609 Dorsomorphin increased thereby diminishing against Our study identified master regulator that enables ameliorate during early stage function. By targeting S100A8-initiated pathway, we may unlock novel therapeutic intervention develop refined strategy
Язык: Английский
Процитировано
1
Frontiers in Pharmacology, Год журнала: 2025, Номер 16
Опубликована: Фев. 13, 2025
Osteoarthritis is a degenerative joint disorder characterized by cartilage degradation, synovial inflammation, and altered subchondral bone structure. Recent insights have identified mitochondrial dysfunction as pivotal factor in OA pathogenesis, contributing to chondrocyte apoptosis, oxidative stress, extracellular matrix degradation. Disruptions dynamics, including impaired biogenesis, mitophagy, metabolic shifts from phosphorylation glycolysis, exacerbate damage promoting the production of reactive oxygen species matrix-degrading enzymes such ADAMTS MMPs. This review explores molecular mechanisms underlying OA, emphasizing its role homeostasis inflammation. Furthermore, it highlights emerging therapeutic strategies targeting pathways, antioxidants, mitophagy enhancers, modulators, potential interventions mitigate disease progression, which offer promising avenues for advancing personalized disease-modifying treatments OA.
Язык: Английский
Процитировано
1
Neural Regeneration Research, Год журнала: 2022, Номер 18(5), С. 996 - 996
Опубликована: Окт. 27, 2022
Nitric oxide (NO)/cyclic guanosine 3',5'-monophosphate (cGMP) signaling has been shown to act as a mediator involved in pain transmission and processing. In this review, we summarize discuss the mechanisms of NO/cGMP pathway chronic pain, including neuropathic bone cancer inflammatory morphine tolerance. The main process cells involves NO activating soluble guanylate cyclase, which leads subsequent production cGMP. cGMP then activates cGMP-dependent protein kinase (PKG), resulting activation multiple targets such opening ATP-sensitive K+ channels. spinal cord evidently induces upregulation downstream molecules, well reactive astrogliosis microglial polarization participate pain. dorsal root ganglion neurons, natriuretic peptide binds particulate guanylyl generating further cGMP/PKG pathway, it also contributes development Upregulation receptors is various models. Notably expression effectors, exerting both algesic analgesic effects These findings suggest that plays constituent role with dual an interesting promising target for therapy.
Язык: Английский
Процитировано
34
Life Sciences, Год журнала: 2023, Номер 322, С. 121666 - 121666
Опубликована: Апрель 7, 2023
Aging is a natural process, characterized by progressive loss of physiological integrity, impaired function, and increased vulnerability to death. For centuries, people have been trying hard understand the process aging find effective ways delay it. However, limited breakthroughs made in anti-aging area. Since hallmarks were summarized 2013, increasing studies focus on role mitochondrial dysfunction aging-related degenerative diseases, such as neurodegenerative osteoarthritis, metabolic cardiovascular diseases. Accumulating evidence indicates that restoring function biogenesis exerts beneficial effects extending lifespan promoting healthy aging. In this paper, we provide an overview changes during summarize advanced therapies for treatment Current challenges future perspectives are proposed novel promising directions research.
Язык: Английский
Процитировано
17