Mitophagy in degenerative joint diseases

Autophagy, Год журнала: 2020, Номер 17(9), С. 2082 - 2092

Опубликована: Сен. 24, 2020

Mitochondrial dysfunction is involved in aging and multiple degenerative diseases, including intervertebral disc degeneration (IVDD) osteoarthritis (OA). Thus, the maintenance of mitochondria homeostasis function important. Mitophagy, a process that selectively clears damaged or dysfunctional through autophagic machinery, functions to maintain mitochondrial quality control homeostasis. IVDD OA are similar joint diseases involving degradation cartilaginous tissues mainly caused by oxidative stress, cell apoptosis extracellular matrix (ECM) degradation. Over past decade, accumulating evidence indicates essential role mitophagy pathogenesis OA. Importantly, strategies regulation exert beneficial effects pre-clinical experiments. Given importance novelty mitophagy, we provide an overview pathways discuss roles We also highlight potential targeting for treatment diseases.Abbreviations: AD: Alzheimer disease; AF: annulus fibrosus; ADORA2A/A2AR: adenosine A2a receptor; AMBRA1: autophagy beclin 1 regulator 1; BMSCs: bone marrow mesenchymal stem cells; BNIP3: BCL2 interacting protein 3; BNIP3L/NIX: BCL2/adenovirus E1B 3-like; CDH6: cadherin 6; CEP: endplates; circRNA: circular RNA; DNM1L/DRP1: dynamin 1-like; ECM: matrix; HIF1A: hypoxia inducible factor 1: alpha subunit; IL1B: interleukin beta; IMM: inner membranes; IVDD: degeneration; MAPK8/JNK: mitogen-activated kinase 8; MFN1: mitofusin MFN2: 2; MIA: monosodium iodoacetate; RHOT/MIRO: ras homolog family member T; MMP: transmembrane potential; CALCOCO2/NDP52: calcium binding coiled-coil domain NFE2L2: nuclear factor: erythroid 2 like NP: nucleus pulposus; OA: osteoarthritis; OPA1: GTPase; OPTN: optineurin; PRKN: parkin RBR E3 ubiquitin ligase; PD: Parkinson PGAM5: PGAM 5; PPARGC1A/PGC-1A: peroxisome proliferator activated receptor: gamma: coactivator alpha; PHF23: PHD finger 23; PINK1: PTEN induced putative ROS: reactive oxygen species; SfMSCs: synovial fluid MSCs; SIRT1: sirtuin SIRT2: SIRT3: SQSTM1/p62: sequestosome TNF: tumor necrosis factor; Ub: ubiquitin; UBL: ubiquitin-like; VDAC: voltage-dependent anion channel.

Язык: Английский

---

NF‐κB signalling pathways in nucleus pulposus cell function and intervertebral disc degeneration

Cell Proliferation, Год журнала: 2021, Номер 54(7)

Опубликована: Май 24, 2021

Intervertebral disc degeneration (IDD) is a common clinical degenerative disease of the spine. A series factors, such as inflammation, oxidative stress and mechanical stress, promote degradation extracellular matrix (ECM) intervertebral discs (IVD), leading to dysfunction structural destruction IVD. Nuclear factor-κB (NF-κB) transcription factor has long been regarded pathogenic IDD. Therefore, NF-κB may be an ideal therapeutic target for As multifunctional functional with roles in variety biological processes, comprehensive understanding function regulatory mechanism IDD pathology will useful development targeted strategies IDD, which can prevent progression reduce potential risks. This review discusses role signalling pathway nucleus pulposus (NP) process understand pathological NP further provide targets that interfere therapy.

Язык: Английский

---

The role of autophagy in bone metabolism and clinical significance

Autophagy, Год журнала: 2023, Номер 19(9), С. 2409 - 2427

Опубликована: Март 2, 2023

The skeletal system is the basis of vertebral body composition, which affords stabilization sites for muscle attachment, protects vital organs, stores mineral ions, supplies places to hematopoietic system, and participates in complex endocrine immune system. Not surprisingly, bones are constantly reabsorbed, formed, remodeled under physiological conditions. Once bone metabolic homeostasis interrupted (including inflammation, tumors, fractures, diseases), rapidly initiates regeneration maintain tissue structure quality. Macroautophagy/autophagy an essential process eukaryotic cells, maintains energy plays a role by controlling molecular degradation organelle renewal. One relatively new observation that mesenchymal osteoblasts, osteoclasts, osteocytes, chondrocytes, vascularization exhibit autophagy, mechanisms targets involved being explored updated. autophagy also emerging degenerative diseases (intervertebral disc degeneration [IVDD], osteoarthritis [OA], etc.) (osteoporosis [OP], osteitis deformans, osteosclerosis). use regulators modulate has benefited regeneration, including MTOR (mechanistic target rapamycin kinase) inhibitors, AMPK activators, phytochemicals. application biomaterials (especially nanomaterials) trigger attractive research direction, can exert superior therapeutic properties from material-loaded molecules/drugs or material's such as shape, roughness, surface chemistry, etc. All these have clinical significance with discovery associated signals, pathways, mechanisms, treatments future.Abbreviations: Δψm: mitochondrial transmembrane potential AMPK: AMP-activated protein kinase ARO: autosomal recessive osteosclerosis ATF4: activating transcription factor 4 ATG: autophagy-related β-ECD: β-ecdysone BMSC: marrow stem cell ER: endoplasmic reticulum FOXO: forkhead box O GC: glucocorticoid HIF1A/HIF-1α: hypoxia inducible 1 subunit alpha HSC: HSP: heat shock IGF1: insulin like growth IL1B/IL-1β: interleukin beta IVDD: intervertebral LPS: lipopolysaccharide MAPK: mitogen-activated MSC: MTOR: mechanistic NP: nucleus pulposus NPWT: negative pressure wound therapy OA: OP: osteoporosis PTH: parathyroid hormone ROS: reactive oxygen species SIRT1: sirtuin SIRT3: 3 SQSTM1/p62: sequestosome TNFRSF11B/OPG: TNF receptor superfamily member 11b TNFRSF11A/RANK: tumor necrosis superfamily, 11a TNFSF11/RANKL: (ligand) 11 TSC1: tuberous sclerosis ULK1: unc-51

Язык: Английский

---

Antioxidant Therapy in Oxidative Stress-Induced Neurodegenerative Diseases: Role of Nanoparticle-Based Drug Delivery Systems in Clinical Translation

Antioxidants, Год журнала: 2022, Номер 11(2), С. 408 - 408

Опубликована: Фев. 17, 2022

Free radicals are formed as a part of normal metabolic activities but neutralized by the endogenous antioxidants present in cells/tissue, thus maintaining redox balance. This balance is disrupted certain neuropathophysiological conditions, causing oxidative stress, which implicated several progressive neurodegenerative diseases. Following neuronal injury, secondary injury progression also caused excessive production free radicals. Highly reactive radicals, mainly oxygen species (ROS) and nitrogen (RNS), damage cell membrane, proteins, DNA, triggers self-propagating inflammatory cascade degenerative events. Dysfunctional mitochondria under stress conditions considered key mediator neurodegeneration. Exogenous delivery holds promise to alleviate regain In this regard, natural synthetic have been evaluated. Despite promising results preclinical studies, clinical translation therapy treat diseases remains elusive. The issues could be their low bioavailability, instability, limited transport target tissue, and/or poor antioxidant capacity, requiring repeated high dosing, cannot administered humans because dose-limiting toxicity. Our laboratory investigating nanoparticle-mediated enzymes address some above issues. Apart from being endogenous, main advantage catalytic mechanism action; hence, they significantly more effective at lower doses detoxifying deleterious effects than nonenzymatic antioxidants. review provides comprehensive analysis potential therapy, challenges translation, role nanoparticles/drug systems play addressing these challenges.

Язык: Английский

---

The Nrf2 antioxidant defense system in intervertebral disc degeneration: Molecular insights

Experimental & Molecular Medicine, Год журнала: 2022, Номер 54(8), С. 1067 - 1075

Опубликована: Авг. 17, 2022

Intervertebral disc degeneration (IDD) is a common degenerative musculoskeletal disorder and recognized as major contributor to discogenic lower back pain. However, the molecular mechanisms underlying IDD remain unclear, therapeutic strategies for are currently limited. Oxidative stress plays pivotal roles in pathogenesis progression of many age-related diseases humans, including IDD. Nuclear factor E2-related 2 (Nrf2) master antioxidant transcription that protects cells against oxidative damage. Nrf2 negatively modulated by Kelch-like ECH-associated protein 1 (Keap1) exerts important effects on progression. Accumulating evidence has revealed can facilitate downstream genes binding response elements (AREs) promoter regions, heme oxygenase-1 (HO-1), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), NADPH quinone dehydrogenase (NQO1). The defense system regulates cell apoptosis, senescence, extracellular matrix (ECM) metabolism, inflammatory nucleus pulposus (NP), calcification cartilaginous endplates (EP) In this review, we aim discuss current knowledge systematically.

Язык: Английский

---

Oxidative stress in intervertebral disc degeneration: Molecular mechanisms, pathogenesis and treatment

Cell Proliferation, Год журнала: 2023, Номер 56(9)

Опубликована: Март 13, 2023

Abstract Low back pain (LBP) is a leading cause of labour loss and disability worldwide, it also imposes severe economic burden on patients society. Among symptomatic LBP, approximately 40% caused by intervertebral disc degeneration (IDD). IDD the pathological basis many spinal degenerative diseases such as herniation stenosis. Currently, therapeutic approaches for mainly include conservative treatment surgical treatment, neither which can solve problem from root terminating process (IVD). Therefore, further exploring pathogenic mechanisms adopting targeted strategies one current research hotspots. complex pathophysiological processes IDD, oxidative stress considered main factor. The delicate balance between reactive oxygen species (ROS) antioxidants essential maintaining normal function survival IVD cells. Excessive ROS levels damage to macromolecules nucleic acids, lipids, proteins cells, affect cellular activities functions, ultimately lead cell senescence or death. This review discusses potential role in understand provides IDD.

Язык: Английский

---

Causes of and Molecular Targets for the Treatment of Intervertebral Disc Degeneration: A Review

Cells, Год журнала: 2022, Номер 11(3), С. 394 - 394

Опубликована: Янв. 24, 2022

Intervertebral disc degeneration (IVDD) is a pathological condition that can lead to intractable back pain or secondary neurological deficits. There no fundamental cure for this condition, and current treatments focus on alleviating symptoms indirectly. Numerous studies have been performed date, the major strategy all of IVDD prevent cell loss due programmed regulated death. Accumulating evidence suggests several types death other than apoptosis, including necroptosis, pyroptosis, ferroptosis, are also involved in IVDD. In study, we discuss molecular pathway each type review literature has identified their role We summarize recent advances targeted therapy at RNA level, modulations through interference regulation non-coding RNAs, preventing subsequent Therefore, causes possible therapeutic targets intervention future direction research field.

Язык: Английский

---

Mitochondrial dysfunction and neurological disorders: A narrative review and treatment overview

Life Sciences, Год журнала: 2023, Номер 334, С. 122257 - 122257

Опубликована: Ноя. 8, 2023

Язык: Английский

---

Mitochondrial quality control in human health and disease

Military Medical Research, Год журнала: 2024, Номер 11(1)

Опубликована: Май 29, 2024

Abstract Mitochondria, the most crucial energy-generating organelles in eukaryotic cells, play a pivotal role regulating energy metabolism. However, their significance extends beyond this, as they are also indispensable vital life processes such cell proliferation, differentiation, immune responses, and redox balance. In response to various physiological signals or external stimuli, sophisticated mitochondrial quality control (MQC) mechanism has evolved, encompassing key like biogenesis, dynamics, mitophagy, which have garnered increasing attention from researchers unveil specific molecular mechanisms. this review, we present comprehensive summary of primary mechanisms functions regulators involved major components MQC. Furthermore, critical regulated by MQC its diverse roles progression systemic diseases been described detail. We discuss agonists antagonists targeting MQC, aiming explore potential therapeutic research prospects enhancing stabilize function.

Язык: Английский

---

The role of oxidative stress in intervertebral disc degeneration: Mechanisms and therapeutic implications

Ageing Research Reviews, Год журнала: 2024, Номер 98, С. 102323 - 102323

Опубликована: Май 9, 2024

Oxidative stress is one of the main driving mechanisms intervertebral disc degeneration(IDD). has been associated with inflammation in disc, cellular senescence, autophagy, and epigenetics cells. It above pathological are closely linked through common hub reactive oxygen species(ROS), promote each other process degeneration development disease. This reveals important role oxidative IDD, importance great potential IDD therapy targeting stress. The efficacy traditional unstable or cannot be maintained. In recent years, due to rise materials science, many bioactive functional have applied treatment combination drugs, satisfactory achieved. At present, research review antioxidant not complete. Based on existing studies, mechanism were summarized this paper, strategies based emerging reviewed.

Язык: Английский

---