Metabolic dysregulation of tricarboxylic acid cycle and oxidative phosphorylation in glioblastoma.

Glioblastoma multiforme (GBM) exhibits genetic alterations that induce the deregulation of oncogenic pathways, thus promoting metabolic adaptation. The modulation of metabolic enzyme activities is necessary to generate nucleotides, amino acids, and fatty acids, which provide energy and metabolic intermediates essential for fulfilling the biosynthetic needs of glioma cells. Moreover, the TCA cycle produces intermediates that play important roles in the metabolism of glucose, fatty acids, or non-essential amino acids, and act as signaling molecules associated with the activation of oncogenic pathways, transcriptional changes, and epigenetic modifications.

Metabolic Roles of HIF1, c-Myc, and p53 in Glioma Cells.

The metabolic reprogramming that promotes tumorigenesis in glioblastoma is induced by dynamic alterations in the hypoxic tumor microenvironment, as well as in transcriptional and signaling networks, which result in changes in global genetic expression. The signaling pathways PI3K/AKT/mTOR and RAS/RAF/MEK/ERK stimulate cell metabolism, either directly or indirectly, by modulating the transcriptional factors p53, HIF1, and c-Myc. The overexpression of HIF1 and c-Myc, master regulators of cellular metabolism, is a key contributor to the synthesis of bioenergetic molecules that mediate glioma cell transformation, proliferation, survival, migration, and invasion by modifying the transcription levels of key gene groups involved in metabolism.

Neuroprotective-Neurorestorative Effects Induced by Progesterone on Global Cerebral Ischemia: A Narrative Review.

Progesterone (P4) is a neuroactive hormone having pleiotropic effects, supporting its pharmacological potential to treat global (cardiac-arrest-related) cerebral ischemia, a condition associated with an elevated risk of dementia. This review examines the current biochemical, morphological, and functional evidence showing the neuroprotective/neurorestorative effects of P4 against global cerebral ischemia (GCI). Experimental findings show that P4 may counteract pathophysiological mechanisms and/or regulate endogenous mechanisms of plasticity induced by GCI.

Role of Glycolytic and Glutamine Metabolism Reprogramming on the Proliferation, Invasion, and Apoptosis Resistance through Modulation of Signaling Pathways in Glioblastoma.

Glioma cells exhibit genetic and metabolic alterations that affect the deregulation of several cellular signal transduction pathways, including those related to glucose metabolism. Moreover, oncogenic signaling pathways induce the expression of metabolic genes, increasing the metabolic enzyme activities and thus the critical biosynthetic pathways to generate nucleotides, amino acids, and fatty acids, which provide energy and metabolic intermediates that are essential to accomplish the biosynthetic needs of glioma cells. In this review, we aim to explore how dysregulated metabolic enzymes and their metabolites from primary metabolism pathways in glioblastoma (GBM) such as glycolysis and glutaminolysis modulate anabolic and catabolic metabolic pathways as well as pro-oncogenic signaling and contribute to the formation, survival, growth, and malignancy of glioma cells.

Transsulfuration pathway: a targeting neuromodulator in Parkinson's disease.

The transsulfuration pathway (TSP) is a metabolic pathway involving sulfur transfer from homocysteine to cysteine. Transsulfuration pathway leads to many sulfur metabolites, principally glutathione, HS, taurine, and cysteine. Key enzymes of the TSP, such as cystathionine β-synthase and cystathionine γ-lyase, are essential regulators at multiple levels in this pathway.