A Critical Kinase Cascade In Neurological Disorders: Pi3K, Akt and Mtor

Abstract

Neurodegenerative disorders lead to disability and death in a significant proportion of the world’s population. However, many disorders of the nervous system remain with limited effective treatments. Kinase pathways in the nervous system that involve phosphoinositide 3-kinase (PI 3-K), protein kinase B (Akt), and the mammalian target of rapamycin (mTOR) offer exciting prospects for the understanding of neurodegenerative pathways and the development of new avenues of treatment. PI 3-K, Akt, and mTOR pathways are vital cellular components that determine cell fate during acute and chronic disorders, such as Huntington’s disease, Alzheimer’s disease, Parkinson’s disease, epilepsy, stroke, and trauma. Yet, the elaborate relationship among these kinases and the variable control of apoptosis and autophagy can lead to unanticipated biological and clinical outcomes. Crucial for the successful translation of PI 3-K, Akt, and mTOR into robust and safe clinical strategies will be the further elucidation of the complex roles that these kinase pathways hold in the nervous system.

A Large Scale Huntingtin Protein Interaction Network Implicates Rho GTPase Signaling Pathways in Huntington Disease

“…Dysregulation of the PI3K pathway is associated with numerous cancers (31), inflammatory diseases (32), and metabolic diseases like diabetes (33). This pathway has also been shown to play a critical role in neurodegenerative diseases such as HD (34,35).…”

Early molecular and behavioral response to lipopolysaccharide in the WAG/Rij rat model of absence epilepsy and depressive-like behavior, involves interplay between AMPK, AKT/mTOR pathways and neuroinflammatory cytokine release

“…Briefly, AKT phosphorylation is generally considered to increase mTOR activity through the TSC complex (Chong et al, 2012;Russo et al, 2012a); however, AKT can inhibit mTORC-1 complex activity by phosphorylating PRAS40 (proline-rich AKT substrate of 40 kDa), Fig. 5.…”

The functions of estrogen receptor beta in the female brain: A systematic review

“…Similarly, mGluRs act as a second messenger in the signalling pathway that modulates synaptic transmission and neuronal excitability, suggesting a potential therapeutic utility in AD, Parkinson disease, schizophrenia, anxiety and depression [65,66]. Consequently, further research into these components may prove to be potential opportunities for treatment for Huntington's disease, AD, epilepsy, and trauma [67,68].…”