Polydopamine Nanoparticles Targeting Ferroptosis Mitigate Intervertebral Disc Degeneration Via Reactive Oxygen Species Depletion, Iron Ions Chelation, and GPX4 Ubiquitination Suppression

Yang, Xiaobin; Chen, Yan; Guo, Jiadong; Li, Jiaxin; Zhang, Pu; Yang, Huan; Rong, Kewei; Zhou, Ting; Fu, Jingke; Zhao, Jie

doi:10.1002/advs.202207216

Cited by 54 publications

(10 citation statements)

References 74 publications

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“…Using genetic variants associated with iron status and IVDD, our two-sample MR analyses showed that iron status had no causal relationships with IVDD. Although it is generally believed that iron status and intervertebral disc degeneration disorders are separate entities,several studies have suggested an association between iron and IVDD [23].…”

Section: Discussionmentioning

confidence: 99%

Mendelian randomization studies do not support the causal relationships between iron status and Intervertebral disc degeneration

Geng,

Wang,

Zhang

et al. 2024

Preprint

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1. Introduction Context:Intervertebral disc degeneration (IVDD) is an important contributor of low back pain, which represents one of the most disabling symptoms within the adult population.Recently, increasing evidence suggests the potential association between iron status and IVDD. However, the causal relationship between these two common diseases remains unclear.We investigated the causal effects of four iron metabolism markers, regular iron supplementation and IVDD. 2. Methods: We conducted a two-sample Mendelian randomization (MR) analysis to assess the causal association between iron status and IVDD[1]. Sensitivity analysis was performed to test for heterogeneity and horizontal pleiotropy. 3. Results The genetically instrumented iron (odds ratio [OR]: 1.03; 95% confidence interval [CI]: 0.97–1.11; P=0.27)； ferritin(OR: 1.17; 95% CI: 0.99–1.38; P=0.07)； Liver iron content (OR: 1.04; 95% CI: 0.98–1.11; P=0.22)；Tranferrein(OR: 0.99; 95% CI: 0.91–1.08; P=0.85)；Tranferrein stautas (OR:1.02; 95% CI: 0.98–1.08; P=0.34)or supplement iron(OR:0.91; 95% CI: 0.79–1.05; P=0.18) showed no causal relationships with IVDD.No pleiotropic bias was found in the MR analyses. As heterogeneity was significant, a random model was used to minimize the effect of heterogeneity. 4. Conclusions No causal associations existed between iron status and IVDD. iron status and IVDD may represent separate entities.

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Section: Discussionmentioning

confidence: 99%

Mendelian randomization studies do not support the causal relationships between iron status and Intervertebral disc degeneration

Geng,

Wang,

Zhang

et al. 2024

Preprint

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“…A recent study showed that a large number of mitochondria are indeed present in NPCs; these mitochondria are typically tubular, highly networked, and hypoxia-responsive 41 . Moreover, a growing body of evidence demonstrates that mitochondrial dysfunction leads to excessive death in NPCs through mechanisms such as apoptosis and ferroptosis 42 – 44 . Consequently, keeping mitochondrial health is essential for maintaining the physiological function of NPCs.…”

Section: Discussionmentioning

confidence: 99%

Involvement of DJ-1 in the pathogenesis of intervertebral disc degeneration via hexokinase 2-mediated mitophagy

Lin,

Wang,

et al. 2024

Exp Mol Med

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Intervertebral disc degeneration (IDD) is an important pathological basis for degenerative spinal diseases and is involved in mitophagy dysfunction. However, the molecular mechanisms underlying mitophagy regulation in IDD remain unclear. This study aimed to clarify the role of DJ-1 in regulating mitophagy during IDD pathogenesis. Here, we showed that the mitochondrial localization of DJ-1 in nucleus pulposus cells (NPCs) first increased and then decreased in response to oxidative stress. Subsequently, loss- and gain-of-function experiments revealed that overexpression of DJ-1 in NPCs inhibited oxidative stress-induced mitochondrial dysfunction and mitochondria-dependent apoptosis, whereas knockdown of DJ-1 had the opposite effect. Mechanistically, mitochondrial translocation of DJ-1 promoted the recruitment of hexokinase 2 (HK2) to damaged mitochondria by activating Akt and subsequently Parkin-dependent mitophagy to inhibit oxidative stress-induced apoptosis in NPCs. However, silencing Parkin, reducing mitochondrial recruitment of HK2, or inhibiting Akt activation suppressed DJ-1-mediated mitophagy. Furthermore, overexpression of DJ-1 ameliorated IDD in rats through HK2-mediated mitophagy. Taken together, these findings indicate that DJ-1 promotes HK2-mediated mitophagy under oxidative stress conditions to inhibit mitochondria-dependent apoptosis in NPCs and could be a therapeutic target for IDD.

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“…Treatment with POCG-PEI600 nanoclusters promoted the phosphorylation of p38 in the MAPK signaling pathway (Figure 23G), leading to the activation of PGC-1𝛼 and subsequent mitochondrial biogenesis. Consequently, an increase in Allergic asthma Nf-ABT-199 [ 379] --≈220 48 -Disc degeneration PDA NPs [ 380] --160 -PDA Fibromyalgia Mo 2 C nanozyme [ 380] --11.445(thickness) -Mo 2 C nanozyme Inflammation HCE-AuNPs [ 326] --3-20 --Mitochondrial oxidative stress TPP-Se-CDs [382] -T P P ≈18.4 ± 0.5 22.3 Se-CDs Mitochondrial protection LC-CNS@NTA [383] --230 ± 10 -Lantana camara Oocyte protection CeO 2 NPs [ 384] ≈10 -Oxidative stress Pt@CNDs [ 221] --3 . 2 ± 0.5 −28.1 ± 0.4 -…”

Section: Other Diseasesmentioning

confidence: 99%

Revitalizing Ancient Mitochondria with Nano‐Strategies: Mitochondria‐Remedying Nanodrugs Concentrate on Disease Control

Long,

Liu,

Nan

et al. 2024

Advanced Materials

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Mitochondria, widely known as the energy factories of eukaryotic cells, have a myriad of vital functions across diverse cellular processes. Dysfunctions within mitochondria serve as catalysts for various diseases, prompting widespread cellular demise. Mounting research on remedying damaged mitochondria indicates that mitochondria constitute a valuable target for therapeutic intervention against diseases. But the less clinical practice and lower recovery rate imply the limitation of traditional drugs, which need a further breakthrough. Nanotechnology has approached favorable regiospecific biodistribution and high efficacy by capitalizing on excellent nanomaterials and targeting drug delivery. Mitochondria‐remedying nanodrugs have achieved ideal therapeutic effects. In this review, we have elucidated the significance of mitochondria in various cells and organs, while also compiling mortality data for related diseases. Correspondingly, nanodrug‐mediate therapeutic strategies and applicable mitochondria‐remedying nanodrugs in disease were detailed, with a full understanding of the roles of mitochondria dysfunction and the advantages of nanodrugs. In addition, the future challenges and directions have been widely discussed. In conclusion, this review provides comprehensive insights into the design and development of mitochondria‐remedying nanodrugs, aiming to help scientists who desire to extend their research fields and engage in this interdisciplinary subject.This article is protected by copyright. All rights reserved

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Polydopamine Nanoparticles Targeting Ferroptosis Mitigate Intervertebral Disc Degeneration Via Reactive Oxygen Species Depletion, Iron Ions Chelation, and GPX4 Ubiquitination Suppression

Cited by 54 publications

References 74 publications

Mendelian randomization studies do not support the causal relationships between iron status and Intervertebral disc degeneration

Mendelian randomization studies do not support the causal relationships between iron status and Intervertebral disc degeneration

Involvement of DJ-1 in the pathogenesis of intervertebral disc degeneration via hexokinase 2-mediated mitophagy

Revitalizing Ancient Mitochondria with Nano‐Strategies: Mitochondria‐Remedying Nanodrugs Concentrate on Disease Control

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