Targeting PTEN in ischemic stroke: From molecular mechanisms to therapeutic potentials

Ischemic stroke remains a leading cause of mortality and disability worldwide, driven by complex pathophysiological mechanisms, including excitotoxicity, oxidative stress, apoptosis, and neuroinflammation. PTEN (Phosphatase and tensin homolog deleted on chromosome 10) plays a crucial role in these processes, influencing key signaling pathways such as PI3K/Akt and mTOR. This review aims to explore PTEN's multifaceted functions in ischemic stroke, examining its interactions with non-coding RNAs, involvement in mitophagy and immune suppression, and overall impact on cellular homeostasis. We will investigate various therapeutic strategies targeting PTEN, including synthetic drugs, natural products, and exosome-based therapies enriched with specific miRNAs. Additionally, we will assess the potential of non-pharmaceutical interventions such as electroacupuncture, exercise, transcranial direct current stimulation (tDCS), and therapeutic hypothermia in modulating PTEN activity to enhance cererbroprotection and functional recovery. By elucidating these aspects, this review aims to inspire and motivate the audience in their research and clinical practice, highlighting PTEN as a promising therapeutic target and paving the way for developing effective treatments for ischemic stroke.