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Current Molecular Medicine

Editor-in-Chief

ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

General Research Article

FBXW7alpha Promotes the Recovery of Traumatic Spinal Cord

Author(s): Hong Zhang and Tao Yang*

Volume 20 , Issue 6 , 2020

Page: [494 - 504] Pages: 11

DOI: 10.2174/1566524020666191223164916

Price: $65

Abstract

Background: White matter damage and neuronal cell death are incurred by spinal cord injury (SCI). FBXW7α, an important mediator of cell division and growth was investigated to explore its role in repairing the traumatic spinal cord in rats. Underlying mechanisms such as oxidative stress and inflammasomes signaling were also studied.

Methods: Spinal cord injury in rats was established by longitudinal surgical incision from the lower to mid-thoracic vertebrae on the backside, followed by 20-g weight placed on the exposed Th12 surface for 30 min. AAV-delivered FBXW7α and -sh-FBXW7α were intrathecally injected into the rat spinal cord. Indices of oxidation, neurotrophic factors, and pyroptosis were measured by Western blot, Elisa, and RT-PCR.

Results: We found the overexpression of FBXW7α in spinal cord rescue neuronal death triggered by the injury. Specifically, the nutritional condition, oxidative stress, and pyroptosis were improved. A synchronization of BNDF and GDNF expression patterns in various groups indicated the secretion of neurotrophic factors affect the outcome of SCI. The SOD1, CAT, and GSH-px were suppressed after trauma but all restored in response to FBXW7α overexpression. Inflammasomes-activated pyroptosis was incurred after the injury, and relevant biomarkers such as GSDMD, caspase-1, caspase- 11, IL-1β, and IL-18 were down-regulated after the introduction of FBXW7α into the injured cord. Additionally, up-regulating FBXW7α also repaired the mitochondria dysfunction.

Conclusion: Our data indicate FBXW7α probably serves as an important molecular target for the therapy of spinal cord injury.

Keywords: FBXW7α, spinal cord injury, pyroptosis, oxidative stress, caspase signaling, inflammasomes.

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