ISSLS Prize Winner

Nasto, Luigi Aurelio; Seo, Hyoung Yeon; Robinson, Andria Rasile; Tilstra, Jeremy S.; Clauson, Cheryl L.; Sowa, Gwendolyn; Ngo, Kevin; Dong, Qing; Pola, Enrico; Lee, Joon Y.; Niedernhofer, Laura J.; Kang, James D.; Robbins, Paul D.; Vo, Nam

doi:10.1097/brs.0b013e31824ee8f7

Cited by 69 publications

(25 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Activation of RelA has been proposed to lead the systemic aging process in mice ( 86 , 87 ), being negligible in the hypothalamus of young mice and progressively increasing, earlier in microglia and later in neuronal cells, as the mice become older ( 12 ). The genetic depletion of one allele of RelA attenuated the behavioral signs of neurodegeneration and extended the healthspan in a progeroid mouse model ( 13 ).…”

Section: Discussionmentioning

confidence: 99%

NF-κB in Innate Neuroprotection and Age-Related Neurodegenerative Diseases

et al. 2015

View full text Add to dashboard Cite

NF-κB factors are cardinal transcriptional regulators of inflammation and apoptosis, involved in the brain programing of systemic aging and in brain damage. The composition of NF-κB active dimers and epigenetic mechanisms modulating histone acetylation, finely condition neuronal resilience to brain insults. In stroke models, the activation of NF-κB/c-Rel promotes neuroprotective effects by transcription of specific anti-apoptotic genes. Conversely, aberrant activation of NF-κB/RelA showing reduced level of total acetylation, but site-specific acetylation on lysine 310, triggers the expression of pro-apoptotic genes. Constitutive knockout of c-Rel shatters the resilience of substantia nigra (SN) dopaminergic (DA) neurons to aging and induces a parkinsonian like pathology in mice. c-rel−/− mice show increased level of aberrantly acetylated RelA in the basal ganglia, neuroinflammation, accumulation of alpha-synuclein, and iron. Moreover, they develop motor deficits responsive to l-DOPA treatment and associated with loss of DA neurons in the SN. Here, we discuss the effect of unbalanced activation of RelA and c-Rel during aging and propose novel challenges for the development of therapeutic strategies in neurodegenerative diseases.

show abstract

Section: Discussionmentioning

confidence: 99%

NF-κB in Innate Neuroprotection and Age-Related Neurodegenerative Diseases

et al. 2015

View full text Add to dashboard Cite

show abstract

“…The NF-κB signalling pathway is significantly correlated with the process of IDD. Inhibiting the activation of NF-κB can significantly retard the degree of disc degeneration [13, 28]. It was also reported that the SDF-1/CXCR4 axis induces apoptosis of human degenerative NPCs via the NF-κB pathway [29].…”

Section: Discussionmentioning

confidence: 99%

Hemeoxygenase-1 Suppresses IL-1β-Induced Apoptosis Through the NF-κB Pathway in Human Degenerative Nucleus Pulposus Cells

Zhu

Jiang

Cheng

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Nucleus pulposus cell (NPC) apoptosis is the main factor in intervertebral disc degeneration (IDD); thus, inhibiting the excessive apoptosis of nucleus pulposus cells may be a potential way to alleviate IDD. The effect of Hemeoxygenase-1 (HO-1) on human NPC apoptosis has never been reported. Our study aimed to investigate the effect and mechanism of HO-1 on apoptosis in human degenerative NPCs. Methods: Nucleus pulposus tissues were collected from patients with lumbar vertebral fracture (LVF) and IDD. The expression of HO-1 and P65 in intervertebral discs was determined using immunohistochemistry and western blot analysis. Apoptosis of human nucleus pulposus cells was quantified by flow cytometric analysis. A recombinant lentiviral vector overexpressing HO-1 and HO-1-siRNA was used to promote or silence the expression of HO-1 in nucleus pulposus cells. The NF-κB inhibitor PDTC was used to inhibit the NF-κB pathway. Results: Our study demonstrated that compared with normal samples, IDD samples showed down-regulation of HO-1 expression and up-regulation of P65 expression. Overexpression of HO-1 inhibited the increase in nucleus pulposus cell apoptosis after IL-1β treatment and simultaneously inhibited the expression of p-P65. Furthermore, after treatment with PDTC, the number of apoptotic cells was significantly decreased with or without overexpression of HO-1. Conclusion: HO-1 might play a significant role in IDD, and HO-1 protected degenerative human NPCs against apoptosis induced by IL-1β through the NF-κB pathway. These findings would aid in the development of novel therapeutic approaches for IDD treatment.

show abstract

“…For example, it was found that GDF-5 was essential for the normal lamellar architecture of the AF and the structure of the NP (Li et al ., 2004), and that a deletion of type IX collagen led to premature onset of IVD degeneration (Boyd et al ., 2008). Recently, the DNA repair deficient mouse model of accelerated aging, which had been reported to exhibit age-related IVD degeneration, was used to explore the role of the NFκB signalling pathway in the onset of age-dependent degenerative changes (Nasto et al ., 2012). …”

Section: Preclinical Modelsmentioning

confidence: 99%

Challenges and strategies in the repair of ruptured annulus fibrosus

Guterl¹,

See²,

Blanquer³

et al. 2013

eCM

188

195

View full text Add to dashboard Cite

Lumbar discectomy is the surgical procedure most frequently performed for patients suffering from low back pain and sciatica. Disc herniation as a consequence of degenerative or traumatic processes is commonly encountered as the underlying cause for the painful condition. While discectomy provides favourable outcome in a majority of cases, there are conditions where unmet requirements exist in terms of treatment, such as large disc protrusions with minimal disc degeneration; in these cases, the high rate of recurrent disc herniation after discectomy is a prevalent problem. An effective biological annular repair could improve the surgical outcome in patients with contained disc herniations but otherwise minor degenerative changes. An attractive approach is a tissue-engineered implant that will enable/stimulate the repair of the ruptured annulus. The strategy is to develop three-dimensional scaffolds and activate them by seeding cells or by incorporating molecular signals that enable new matrix synthesis at the defect site, while the biomaterial provides immediate closure of the defect and maintains the mechanical properties of the disc. This review is structured into (1) introduction, (2) clinical problems, current treatment options and needs, (3) biomechanical demands, (4) cellular and extracellular components, (5) biomaterials for delivery, scaffolding and support, (6) pre-clinical models for evaluation of newly developed cell-and material-based therapies, and (7) conclusions. This article highlights that an interdisciplinary approach is necessary for successful development of new clinical methods for annulus fibrosus repair. This will benefit from a close collaboration between research groups with expertise in all areas addressed in this review.

show abstract

ISSLS Prize Winner

Cited by 69 publications

References 44 publications

NF-κB in Innate Neuroprotection and Age-Related Neurodegenerative Diseases

NF-κB in Innate Neuroprotection and Age-Related Neurodegenerative Diseases

Hemeoxygenase-1 Suppresses IL-1β-Induced Apoptosis Through the NF-κB Pathway in Human Degenerative Nucleus Pulposus Cells

Challenges and strategies in the repair of ruptured annulus fibrosus

Contact Info

Product

Resources

About