title: Mitochondrial Mechanisms of Neuronal Cell Death: Potential Therapeutics.
abstract: Mitochondria lie at the crossroads of neuronal survival and cell death. They play important roles in cellular bioenergetics, control intracellular Ca2+homeostasis, and participate in key metabolic pathways. Mutations in genes involved in mitochondrial quality control cause a myriad of neurodegenerative diseases. Mitochondria have evolved strategies to kill cells when they are not able to continue their vital functions. This review provides an overview of the role of mitochondria in neurologic disease and the cell death pathways that are mediated through mitochondria, including their role in accidental cell death, the regulated cell death pathways of apoptosis and parthanatos, and programmed cell death. It details the current state of parthanatic cell death and discusses potential therapeutic strategies targeting initiators and effectors of mitochondrial-mediated cell death in neurologic disorders.
authors.affiliation: Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205; email: tdawson@jhmi.edu , vdawson@jhmi.edu.|Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.|Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.|Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.|Adrienne Helis Malvin Medical Research Foundation, New Orleans, Louisiana 70130.
authors.forename: Ted M
authors.initials: TM
authors.lastname: Dawson
authors.affiliation: Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205; email: tdawson@jhmi.edu , vdawson@jhmi.edu.|Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.|Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.|Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.|Adrienne Helis Malvin Medical Research Foundation, New Orleans, Louisiana 70130.|Diana Helis Henry Medical Research Foundation, New Orleans, Louisiana 70130.
authors.forename: Valina L
authors.initials: VL
authors.lastname: Dawson
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology*; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D020521:Stroke / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism
chemical_list: D000975:Antioxidants
keywords: apoptosis; apoptosis-inducing factor; neurodegeneration; parthanatos; poly (ADP-ribose) polymerase; stroke