Energy, Enzymes, and the Brain: From Cellular Pathways to Therapeutic Pharmacology in Neurological And Neurodegenerative Disorders

Neurodegenerative disorders are pressing global health challenges that stem from progressive neuronal dysfunction and loss. While the central roles of mitochondria in energy production, redox balance, and apoptosis have long been recognized in the context of these conditions, emerging research highlights a fascinating new player: the cytochrome P450 (CYP) superfamily, traditionally studied in hepatic drug metabolism, but now understood as an integral contributor to brain physiology.Recent advances reveal that brain-expressed CYP isoforms regulate neurosteroidogenesis, cholesterol metabolism, lipid signaling, and oxidative stress—all processes that intersect with mitochondrial pathways and are crucial for neural health. Mitochondrial dysfunction is a hallmark of neurodegeneration, leading to impaired bioenergetics, disturbed calcium handling, excessive reactive oxygen species, and cell death. Meanwhile, dysfunction or altered expression in CYP enzymes has been linked to disrupted neurovascular regulation, perturbed brain drug metabolism, and variability in therapeutic outcomes, especially considering individual pharmacogenomic differences.Moreover, the crosstalk between mitochondria and CYPs, particularly in redox signaling, lipid metabolism, and cellular adaptation to stress, is increasingly recognized as a critical factor in maintaining neural health. This Research Topic aims to bring together studies addressing mitochondrial an/or CYP-mediated mechanisms in brain health and disease. We invite contributions focusing on molecular, cellular, translational, and pharmacological perspectives to clarify the interplay between these organellar systems, their dysregulation in neurological and neurodegenerative disorders, and opportunities for therapeutic targeting.This collection welcome (but is not limited to) the following topics:Mitochondrial Dynamics in Neurodegeneration: Mechanisms of fission, fusion, and mitophagy, and their implications for neural homeostasis, cell death, and pharmacological intervention.Brain Cytochrome P450 Enzymes: Regulation, expression, and neuropharmacological roles in neurosteroidogenesis, lipid, and cholesterol metabolism.Redox Signaling and Organelle Interactions: How mitochondrial ROS and CYP-mediated oxidative pathways influence drug response and neurodegenerative processes.Neurovascular and Blood-Brain Barrier Regulation: The role of mitochondrial and CYP function in maintaining vascular integrity and impacting CNS drug delivery.CYPs and CNS Drug Metabolism: Effects on pharmacokinetics, pharmacodynamics, individual drug response, and the design of neuropharmacological therapies.Cellular Stress and Drug Response: Mitochondrial and CYP contributions to neuronal and glial adaptation to stress, including implications for neuroprotective strategies.Neuropharmacological Targeting: Discovery and development of small molecules, gene therapies, and clinical approaches aimed at modulating mitochondrial and CYP activity.Diagnostic and Therapeutic Biomarkers: Advancements in identifying mitochondrial and CYP-related biomarkers for early detection and therapeutic monitoring in neurological diseases. Topic editors: Pradeepraj Durairaj, Dhananjay Yadav Source: https://www.frontiersin.org/research-topics/73324/energy-enzymes-and-the-brain-from-cellular-pathways-to-therapeutic-pharmacology-in-neurological-and-neurodegenerative-disorders