title: Mitochondrial dysfunction in amyotrophic lateral sclerosis - a valid pharmacological target?
abstract: Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease characterized by the selective death of upper and lower motor neurons which ultimately leads to paralysis and ultimately death. Pathological changes in ALS are closely associated with pronounced and progressive changes in mitochondrial morphology, bioenergetics and calcium homeostasis. Converging evidence suggests that impaired mitochondrial function could be pivotal in the rapid neurodegeneration of this condition. In this review, we provide an update of recent advances in understanding mitochondrial biology in the pathogenesis of ALS and highlight the therapeutic value of pharmacologically targeting mitochondrial biology to slow disease progression.
authors.affiliation: Centre for Neuroscience, Discipline of Medical Biochemistry, Flinders Medical Science and Technology, School of Medicine, Flinders University, Adelaide, SA, Australia.
authors.forename: H
authors.initials: H
authors.lastname: Muyderman
authors.forename: T
authors.initials: T
authors.lastname: Chen
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D016923:Cell Death / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology; D005978:Glutathione / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D058990:Molecular Targeted Therapy / Q000379:methods*; D009154:Mutation; D018384:Oxidative Stress / Q000502:physiology; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; C000606290:SOD1 protein, human; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D005978:Glutathione; D002118:Calcium
keywords: SOD-1; TDP-43; amyotrophic lateral sclerosis; cell death; mitochondria; therapeutic