SIRT1: An Emerging Role in Regulated Cell Death in Ischemic Stroke

Area of Science:

• Neuroscience
• Molecular Biology
• Biochemistry

Background:

• Ischemic stroke (IS) is a leading cause of disability with limited therapeutic options.
• Sirtuin 1 (SIRT1) is a deacetylase crucial for cellular processes implicated in IS pathogenesis.
• SIRT1 regulates neuroinflammation, oxidative stress, and various forms of regulated cell death (RCD).

Purpose of the Study:

• To review the role of SIRT1 in the pathophysiology of ischemic stroke.
• To explore the mechanisms by which SIRT1 influences different cell death pathways in IS.
• To discuss the therapeutic potential and challenges of SIRT1 modulators for IS treatment.

Main Methods:

• Literature review of studies on SIRT1 in ischemic stroke.
• Analysis of SIRT1's molecular mechanisms in neuroinflammation and cell death.
• Examination of preclinical and clinical data on SIRT1 modulators.

Main Results:

• SIRT1 modulates key pathways in IS, including NF-κB, FoxO, eNOS, NOX, and inflammasomes.
• SIRT1 influences apoptosis, ferroptosis, pyroptosis, necroptosis, and other cell death forms in IS.
• SIRT1 modulators like resveratrol demonstrate neuroprotective effects, but face challenges like BBB permeability.

Conclusions:

• SIRT1 is a critical regulator in ischemic stroke, impacting multiple pathophysiological processes.
• Targeting SIRT1 offers therapeutic promise for IS, with several modulators showing efficacy.
• Further research is needed to overcome drug delivery and specificity challenges for clinical translation of SIRT1 modulators in IS.