Selective Autophagy Receptor NBR1 Retards Nucleus Pulposus Cell Senescence by Directing the Clearance of SRBD1

International Journal of Biological Sciences, 2024 · DOI: 10.7150/ijbs.90186 · Published: January 1, 2024

Simple Explanation

This study investigates the role of NBR1, a selective autophagy receptor, in intervertebral disc degeneration (IDD). The study found that NBR1 is reduced in IDD. NBR1 retards cellular senescence and senescence-associated secretory phenotype (SASP) of nucleus pulposus cells (NPCs), primarily through its autophagy-dependent function. NBR1 knockdown leads to the accumulation of S1 RNA-binding domain-containing protein 1 (SRBD1), which triggers cellular senescence via AKT1/p53 and RB/p16 pathways, and promotes SASP via NF-κβ pathway in NPCs.

Study Duration

Not specified

Participants

45 patients with spinal deformities, thoracolumbar vertebral fractures, or intervertebral disc degeneration

Evidence Level

In vivo and in vitro experimental verification

Key Findings

1
NBR1 expression is downregulated in degenerative nucleus pulposus cells (NPCs) in human and rat models of intervertebral disc degeneration (IDD).
2
NBR1 retards the senescent phenotypes of NPCs, promoting ECM anabolism and inhibiting ECM catabolism.
3
NBR1 regulates senescent phenotypes via its selective autophagy-dependent function, specifically through the UBA domain.

Research Summary

This study demonstrates the depletion of the selective autophagy receptor NBR1 in NPCs during the degeneration process, leading to the buildup of SRBD1 within NPCs, thereby accelerating NPCs senescence and initiating IDD. The strategy based on the NBR1/SRBD1 regulatory axis for targeted elimination of detrimental molecules presents a novel outlook for the management of IDD. The absence of the selective autophagy receptor NBR1 in degenerated NPCs, leading to the induction of senescence in NPCs through the inhibition of autophagic degradation of SRBD1 suggests a potential therapeutic strategy for modulating NPCs senescence and IDD.

Practical Implications

Therapeutic Target for IDD

Targeting the NBR1/SRBD1 axis offers a potential therapeutic strategy for modulating NPCs senescence and IDD, providing novel insights for treatment.

Biomarker for Senescence

SRBD1 holds promise as a potential biomarker for senescence, as it accumulates significantly in NPCs with impaired selective autophagy and mediates cellular senescence.

Selective Autophagy in IDD

The study highlights the distinctive expression pattern of the selective autophagy receptor NBR1 in IDD, emphasizing the importance of selective autophagy mechanisms in the progression of IDD.

Study Limitations

1
The precise expression and mechanistic roles of additional proteins involved in selective autophagy, such as NDP52 and OPTN, in the context of IDD remain incompletely understood.
2
The specific mechanisms through which SRBD1 influences cellular senescence are yet to be determined, requiring further clarification to ascertain the potential implication of its RNA-binding function.
3
The study focuses on the NBR1/SRBD1 axis, and further research is needed to explore other potential pathways and molecules involved in the complex process of IDD.

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