Advances in Biology & Earth Sciences

Distinct environmental stressors such as hypoxia, ischemia and non-ionizing electromagnetic fields (EMF) can substantially alter the metabolism of neural cells. In this context, pyruvate kinase (PK) signaling pathway which serves as a key enzymatic modulator of glycolysis and other metabolic cascades is highly sensitive to these stress factors. According to in vivo studies, while the cortex and hippocampus reveal a noticeable drop in PK activity, the brainstem regions display a relative resilience or compensatory adaptation in response to stressors. The vulnerability also is affected by developmental stages, as the brain of neonates show a persistent suppression of PK activity in contrast to adult brains that reveal compensatory mechanisms. Mechanistically, hypoxia/ischemia and EMF can induce oxidative stress, stabilize HIF-1α and stimulate a shift in PK isoenzyme expression. As a result, neural cells might survive or undergo processes such as apoptosis or pyroptosis. The current review attempts to shed light on regulation of PK pathway under environmental stress, underlying the structural heterogeneity, developmental sensitivity and molecular adaptations. This information underscores the role of PK as a biomarker of neural damages, while it might also be a potential target of intervention in the future.