title: The role of oxidative stress in degeneration of the neuromuscular junction in amyotrophic lateral sclerosis.
abstract: Amyotrophic lateral sclerosis (ALS) is characterized by the progressive loss of motoneurons and degradation of the neuromuscular junctions (NMJ). Consistent with the dying-back hypothesis of motoneuron degeneration the decline in synaptic function initiates from the presynaptic terminals in ALS. Oxidative stress is a major contributory factor to ALS pathology and affects the presynaptic transmitter releasing machinery. Indeed, in ALS mouse models nerve terminals are sensitive to reactive oxygen species (ROS) suggesting that oxidative stress, along with compromised mitochondria and increased intracellular Ca(2+) amplifies the presynaptic decline in NMJ. This initial dysfunction is followed by a neurodegeneration induced by inflammatory agents and loss of trophic support. To develop effective therapeutic approaches against ALS, it is important to identify the mechanisms underlying the initial pathological events. Given the role of oxidative stress in ALS, targeted antioxidant treatments could be a promising therapeutic approach. However, the complex nature of ALS and failure of monotherapies suggest that an antioxidant therapy should be accompanied by anti-inflammatory interventions to enhance the restoration of the redox balance.
authors.affiliation: Molecular Brain Research Laboratory, Department of Neurobiology, A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland Kuopio, Finland ; Experimental Neurology - Laboratory of Neurobiology, Department of Neurosciences, Vesalius Research Center, KULeuven - University of Leuven Leuven, Belgium.
authors.forename: Eveliina
authors.initials: E
authors.lastname: Pollari
authors.affiliation: Molecular Brain Research Laboratory, Department of Neurobiology, A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland Kuopio, Finland.
authors.forename: Gundars
authors.initials: G
authors.lastname: Goldsteins
authors.affiliation: Cell Biology Laboratory, Department of Neurobiology, A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland Kuopio, Finland.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Bart
authors.affiliation: Molecular Brain Research Laboratory, Department of Neurobiology, A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland Kuopio, Finland.
authors.forename: Jari
authors.initials: J
authors.lastname: Koistinaho
authors.affiliation: Cell Biology Laboratory, Department of Neurobiology, A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland Kuopio, Finland ; Laboratory of Neurobiology, Department of Physiology, Kazan Federal University Kazan, Russia.
authors.forename: Rashid
authors.initials: R
authors.lastname: Giniatullin
keywords: ALS; ROS; neurodegeneration; neuromuscular junction; oxidative stress