Mitochondria and reactive oxygen species in brain development and pediatric brain tumors

Main Article Content

Anshu Malhotra Nicholas W. Eyrich Chad R. Potts M. Hope Robinson Anna Marie Kenney

Abstract

Pediatric brain tumors, such as medulloblastomas, glioma, and ependymoma, are among the most common causes of cancer death in children, and patients that survive the current treatment paradigm (surgery, chemotherapy, and radiation) face lifelong side effects.  Increased understanding of the biological underpinnings of these tumors, which often occur as a result of aberrant regulation of brain developmental signaling pathways, is urgently needed in order to develop treatments that will improve survival and quality of life.   Approximately 30% of medulloblastomas are characterized by activation of the Sonic hedgehog (Shh) signaling pathway and its downstream effectors.  These tumors are thought to arise from cerebellar granule neuron precursors (CGNPs), whose rapid proliferation during development requires Shh signaling. In recent years there has been a resurgence of interest in how metabolism in cancer could represent a novel therapeutic target.  It has been shown that medulloblastomas are heavily dependent upon glycolysis and fatty acid synthesis.  More recent studies have shown that Shh induces mitochondrial fragmentation in proliferating medulloblastoma cells. Mitochondria are regulated by and involved in reactive oxygen species (ROS) production and function.  ROS are implicated in many processes associated with cancer growth and progression, including inflammation, vascularization, proliferation, and apoptosis. In this review, we trace the evolution of mitochondria from their prokaryotic ancestor up to their present-day role. We highlight the proteins that regulate mitochondrial biogenesis and the concurrent metabolic processes leading to ROS production and we discuss implications for mitochondrial biogenesis and ROS activity for brain development and cancer. 

Article Details

How to Cite
MALHOTRA, Anshu et al. Mitochondria and reactive oxygen species in brain development and pediatric brain tumors. Medical Research Archives, [S.l.], v. 5, n. 8, aug. 2017. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/1401>. Date accessed: 28 mar. 2024.
Keywords
medulloblastoma; metabolism; cancer; brain development
Section
Review Articles

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