Title:Targeting Abnormal PI3K/AKT/mTOR Signaling in Intracerebral Hemorrhage:
A Systematic Review on Potential Drug Targets and Influences
of Signaling Modulators on Other Neurological Disorders
Volume: 17
Issue: 3
Author(s): Kuldeep Singh Jadaun, Aarti Sharma, Ehraz Mehmood Siddiqui and Sidharth Mehan*
Affiliation:
- Neuropharmacology Division, Department of Pharmacology, ISF College of Pharmacy, Moga, Punjab, India
Keywords:
PI3K/AKT/mTOR signaling, intracerebral hemorrhage, neurodegeneration, neuronal metabolism, neuroprotection, drug targets.
Abstract: PI3K/AKT/mTOR (phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin)
signaling pathway is an important signal transduction pathway mediated by enzyme-linked
receptors with many biological functions in mammals. This pathway modulates the epigenetic modification
of DNA and target gene histones and plays a significant role in regulating biological activity,
disease progression, oncogenesis, and cancer progression. PI3K/AKT/mTOR signaling pathway involves
and mediates many cellular processes such as nutrient uptake, proliferation, anabolic reactions,
and cell survival. Several studies have shown that PI3K/AKT/mTOR has been a promising therapeutic
approach to intracerebral hemorrhage (ICH). ICH is characterized by the progressive development of
hematoma, which leads to the structural destabilization of the neurons and glial cells, leading to neuronal
deformation, further contributing to mitochondrial dysfunction, membrane depolarization, oligaemia,
and neurotransmitter imbalance. Partial suppression of cell metabolism and necrosis can occur,
depending on the degree of mitochondrial dysfunction. Therefore in the following review, we discuss
whether or not the activation of the PI3K/AKT/mTOR signaling pathway could minimize neuronal
dysfunction following ICH. We further elaborate the review by discussing the updated pathophysiology
of brain hemorrhage and the role of molecular targets in other neurodegenerative diseases.
This review provides current approachable disease treatment in various disease states, single and dual
PI3K/AKT/mTOR signaling pathway modulators.