There are many evidences implicating glutamatergic toxicity as a contributory factor in the selective neuronal injury occurring in amyotrophic lateral sclerosis (ALS). This neurodegenerative disorder is characterized by the progressive loss of motor neurons, whose pathogenesis is thought to involve Ca2+ influx mediated by alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionate receptors (AMPARs). In the present study we report alterations in the AMPARs function in a transgenic mouse-model of the human SOD1(G93A) familial ALS. Compared with those expressed in motor neurons carrying the human wild type gene, AMPAR-gated channels expressed in motor neurons carrying the human mutant gene exhibited modified permeability, altered agonist cooperativity between the sites involved in the process of channel opening and were responsible for slower spontaneous synaptic events. These observations demonstrate that the SOD1(G93A) mutation induces changes in AMPAR functions which may underlie the increased vulnerability of motor neurons to glutamatergic excitotoxicity in ALS. (C) 2003 IBRO. Published by Elsevier Ltd. All rights reserved.

Pieri, M., Gaetti, C., Spalloni, A., Cavalcanti, S., Mercuri, N., Bernardi, G., et al. (2003). alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionate receptors in spinal cord motor neurons are altered in transgenic mice overexpressing human Cu,Zn superoxide dismutase (Gly(93) -> Ala) mutation. NEUROSCIENCE, 122(1), 47-58 [10.1016/j.neuroscience.2003.07.003].

alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionate receptors in spinal cord motor neurons are altered in transgenic mice overexpressing human Cu,Zn superoxide dismutase (Gly(93) -> Ala) mutation

PIERI, MASSIMO;MERCURI, NICOLA BIAGIO;BERNARDI, GIORGIO;ZONA, CRISTINA
2003

Abstract

There are many evidences implicating glutamatergic toxicity as a contributory factor in the selective neuronal injury occurring in amyotrophic lateral sclerosis (ALS). This neurodegenerative disorder is characterized by the progressive loss of motor neurons, whose pathogenesis is thought to involve Ca2+ influx mediated by alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionate receptors (AMPARs). In the present study we report alterations in the AMPARs function in a transgenic mouse-model of the human SOD1(G93A) familial ALS. Compared with those expressed in motor neurons carrying the human wild type gene, AMPAR-gated channels expressed in motor neurons carrying the human mutant gene exhibited modified permeability, altered agonist cooperativity between the sites involved in the process of channel opening and were responsible for slower spontaneous synaptic events. These observations demonstrate that the SOD1(G93A) mutation induces changes in AMPAR functions which may underlie the increased vulnerability of motor neurons to glutamatergic excitotoxicity in ALS. (C) 2003 IBRO. Published by Elsevier Ltd. All rights reserved.
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/09
Settore MED/26 - Neurologia
eng
Con Impact Factor ISI
ALS; Excitotoxicity; Glutamate receptors; Patch-clamp
alanine; AMPA receptor; copper; glycine; superoxide dismutase; zinc; animal cell; animal tissue; article; controlled study; embryo; female; gene mutation; gene overexpression; human; male; mouse; nonhuman; permeability; priority journal; protein function; protein localization; spinal cord motoneuron; spinal cord nerve cell; synapse; transgenic mouse; wild type; Alanine; Amyotrophic Lateral Sclerosis; Animals; Cell Culture Techniques; Disease Models, Animal; Electrophysiology; Glycine; Immunohistochemistry; Mice; Mice, Transgenic; Motor Neurons; Mutation; Patch-Clamp Techniques; Receptors, AMPA; Spinal Cord; Superoxide Dismutase; Up-Regulation
Pieri, M., Gaetti, C., Spalloni, A., Cavalcanti, S., Mercuri, N., Bernardi, G., et al. (2003). alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionate receptors in spinal cord motor neurons are altered in transgenic mice overexpressing human Cu,Zn superoxide dismutase (Gly(93) -> Ala) mutation. NEUROSCIENCE, 122(1), 47-58 [10.1016/j.neuroscience.2003.07.003].
Pieri, M; Gaetti, C; Spalloni, A; Cavalcanti, S; Mercuri, Nb; Bernardi, G; Longone, P; Zona, C
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/66960
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