mTOR/α-ketoglutarate signaling: impact on brain cell homeostasis under ischemic conditions

Iryna Lushnikova; Olha Kostiuchenko; Magdalena Kowalczyk; Galyna Skibo

doi:10.3389/fncel.2023.1132114

mTOR/α-ketoglutarate signaling: impact on brain cell homeostasis under ischemic conditions

Front Cell Neurosci. 2023 May 11:17:1132114. doi: 10.3389/fncel.2023.1132114. eCollection 2023.

Authors

Iryna Lushnikova¹, Olha Kostiuchenko^{1

2}, Magdalena Kowalczyk², Galyna Skibo¹

Affiliations

¹ Department of Cytology, Bogomoletz Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine.
² Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland.

Abstract

The multifunctional molecules mechanistic target of rapamycin (mTOR) and α-ketoglutarate (αKG) are crucial players in the regulatory mechanisms that maintain cell homeostasis in an ever-changing environment. Cerebral ischemia is associated primarily with oxygen-glucose deficiency (OGD) due to circulatory disorders. Upon exceeding a threshold of resistance to OGD, essential pathways of cellular metabolism can be disrupted, leading to damage of brain cells up to the loss of function and death. This mini-review focuses on the role of mTOR and αKG signaling in the metabolic homeostasis of brain cells under OGD conditions. Integral mechanisms concerning the relative cell resistance to OGD and the molecular basis of αKG-mediated neuroprotection are discussed. The study of molecular events associated with cerebral ischemia and endogenous neuroprotection is relevant for improving the effectiveness of therapeutic strategies.

Keywords: autophagy; brain ischemia; homeostasis; mTOR; neuroprotection; α-ketoglutarate (αKG).

Publication types

Review

Grants and funding

This work was funded by the National Academy of Sciences of Ukraine. State registration number of work is 0118U007350. This review study was supported by NAWA scholarship program “Solidarni z Ukrainą” and “IBB START” scholarship of the Institute of Biochemistry and Biophysics, Polish Academy of Sciences.