Pharmacological modulation of PI3K/PTEN/Akt/mTOR/ERK signaling pathways in ischemic injury: a mechanistic perspective

Ischemia, also known as ischemia, relates to the reduced blood movement to a cells, muscle group, or organ in the body, culminating in an insufficient amount of oxygen required for cellular metabolism and the maintenance of tissue viability. There are different types of stroke (ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage), and different causes of stroke (e.g., cardioembolic, atherothrombotic, lacunar ischemic strokes, aneurysmal subarachnoid hemorrhage). It also includes other disorders affecting the blood vessels in the brain (e.g., vascular malformations, unruptured aneurysms). Each of these conditions has different characteristics in terms of how common they are and how they are managed. Stroke is the primary and catastrophic clinical presentation of all cerebrovascular diseases. In this review we focused about the importance of PI3K/AKT signaling pathways which are important in the onset of ischemia-reperfusion (I/R) injury. In addition, mTOR, a target that is activated by the PI3K/Akt signaling pathway, is both required and capable of providing enough protection to the heart against harm caused by I/R. Moreover, the signaling pathways that involve PI3K/Akt/Erk/PTEN/mTOR play a crucial role in facilitating the proliferation and maintenance of neurons following an ischemic stroke. The current review summarizes the molecular mechanisms of various signaling pathways in ischemic diseases and suggests targeting its receptors as a preventive approach based on pre-clinical and clinical studies.