The Role of Akt Signalling Pathway in Neurological and Cardiovascular Pathologies

Year 2023, , 95 - 108, 26.06.2023

Akshat Modi , Aahmad Mahoon Dharmeshkumar Modi

https://doi.org/10.26650/EurJBiol.2023.1240220

Abstract

The PI3K/Akt/mTOR signalling pathway plays a crucial role in several biological processes, including cell proliferation, survival, and apoptosis, as well as regulates numerous signalling pathways, including JNK, NF-𝜅B, and ERK pathways. The recent proliferation of signal transduction studies in neurological and cardiovascular diseases/injuries sheds light on Akt-dependent pathogenesis. The downregulation of the Akt signalling pathway 24 hours post-injury prevents neurogenesis and promotes the progression of severe secondary injuries, including neuroinflammation, scar formation, and neuronal and glial necrosis, following traumatic brain and spinal cord injury, suggesting designing therapeutic approaches within a 24-hour window postinjury. Similarly, the downregulation of the Akt signalling pathway in myocardial infarction lowers cardiovascular protection, limits neurovascularization, and inhibits cell survival. Following myocarditis, the Akt signalling network is upregulated, leading to aggravated inflammation, and increased myocardial damage. Also, the upregulation of the PI3K/Akt/mTOR pathway in chordoma promotes tumor progression and invasion, leading to neuronal damage and impaired physiological functions. Future therapeutics that target the aberrant expression of key players in the PI3K/Akt/mTOR signalling pathway present a promising approach to treating several neurological and cardiovascular pathologies. This narrative review discusses the role of PI3K/Akt/mTOR signalling pathway in traumatic central nervous system injuries (brain and spinal cord), cardiac injury (myocardial infarction), inflammatory disease (myocarditis), and rare neurological cancer (chordoma) along with therapeutic targets that are known to prevent worsened outcomes and promote recovery following those conditions.

Keywords

PI3K/Akt/mTOR Signalling Pathway, Traumatic Spinal Cord Injury, Traumatic Brain Injury, Myocardial Infarction, Myocarditis, Chordoma.

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