Sertad1 Induces Neurological Injury after Ischemic Stroke via the CDK4/p-Rb Pathway

Area of Science:

• Neuroscience
• Molecular Biology
• Pathology

Background:

• SERTA domain-containing protein 1 (Sertad1) is implicated in neuronal death in DNA damage and Alzheimer's disease models.
• The specific role of Sertad1 in ischemic/hypoxic neurological injury is not well understood.

Purpose of the Study:

• To investigate the role and mechanism of Sertad1 in ischemic/hypoxic neurological injury.
• To determine Sertad1's involvement in neuronal apoptosis and cell death pathways.

Main Methods:

• Utilized a mouse middle cerebral artery occlusion and reperfusion model for in vivo studies.
• Employed oxygen-glucose deprivation/reoxygenation (OGD/R) in HT22 cells for in vitro experiments.
• Performed Sertad1 knockdown and overexpression studies, alongside Western blotting and CDK4 inhibitor treatment.

Main Results:

• Sertad1 expression was upregulated in both in vivo and in vitro models of ischemic/hypoxic injury.
• Sertad1 knockdown reduced infarct volume, neurological deficits, and neuronal apoptosis.
• Sertad1 knockdown inhibited the expression of p-Rb, B-Myb, and Bim, while overexpression exacerbated injury.
• Sertad1 directly binds to CDK4, and a CDK4 inhibitor reversed Sertad1-induced cell death and protein expression changes.

Conclusions:

• Sertad1 significantly contributes to ischemic/hypoxic neurological injury.
• Sertad1 promotes neuronal death by activating the CDK4/p-Rb pathway.
• Targeting Sertad1 or the CDK4/p-Rb pathway may offer therapeutic benefits for ischemic stroke.