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Review
. 2024 Feb 1;27(2):pyae010.
doi: 10.1093/ijnp/pyae010.

PI3K-AKT/mTOR Signaling in Psychiatric Disorders: A Valuable Target to Stimulate or Suppress?

Yan Chen  1 , Wei Guan  2 , Mei-Lan Wang  1 , Xiao-Yun Lin  1
Affiliations
Review

PI3K-AKT/mTOR Signaling in Psychiatric Disorders: A Valuable Target to Stimulate or Suppress?

Yan Chen et al. Int J Neuropsychopharmacol. .

Abstract

Economic development and increased stress have considerably increased the prevalence of psychiatric disorders in recent years, which rank as some of the most prevalent diseases globally. Several factors, including chronic social stress, genetic inheritance, and autogenous diseases, lead to the development and progression of psychiatric disorders. Clinical treatments for psychiatric disorders include psychotherapy, chemotherapy, and electric shock therapy. Although various achievements have been made researching psychiatric disorders, the pathogenesis of these diseases has not been fully understood yet, and serious adverse effects and resistance to antipsychotics are major obstacles to treating patients with psychiatric disorders. Recent studies have shown that the mammalian target of rapamycin (mTOR) is a central signaling hub that functions in nerve growth, synapse formation, and plasticity. The PI3K-AKT/mTOR pathway is a critical target for mediating the rapid antidepressant effects of these pharmacological agents in clinical and preclinical research. Abnormal PI3K-AKT/mTOR signaling is closely associated with the pathogenesis of several neurodevelopmental disorders. In this review, we focused on the role of mTOR signaling and the related aberrant neurogenesis in psychiatric disorders. Elucidating the neurobiology of the PI3K-AKT/mTOR signaling pathway in psychiatric disorders and its actions in response to antidepressants will help us better understand brain development and quickly identify new therapeutic targets for the treatment of these mental illnesses.

Keywords: Depression; PI3K-AKT; Psychiatric disorders; Signaling pathway; Targets; mTOR.

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Figures

Graphical Abstract
Graphical Abstract
Figure 1.
Figure 1.
Biological factors participated in the development of psychiatric disorders.
Figure 2.
Figure 2.
The screening process of articles about PI3K-AKT/mTOR signaling in psychiatric disorders.
Figure 3.
Figure 3.
The structure of mTOR protein molecule.
Figure 4.
Figure 4.
Domain structure of mTOR and components of mTORC1 and mTORC2.
Figure 5.
Figure 5.
mTOR signaling pathway has a close relation with many physiological processes of the nervous system, including neural development and neurogenesis, formation and maintenance of synapses, axon regeneration, remyelination, learning and memory.
Figure 6.
Figure 6.
Neuroplasticity as a convergent mechanism for antidepressants. Specifically, antidepressants induced AMPAR activation that in turn potentiated BDNF-TrkB and mTOR signaling, thus upregulating the expression of neuroplasticity-related genes and protein synthesis of synaptic components.
Figure 7.
Figure 7.
The effects of AMPA receptor modulators on mTOR and BDNF expression during the procedure of ketamine exerting antidepressant effects.
See this image and copyright information in PMC

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