Spinal and bulbar muscular atrophy (SBMA) is a neuromuscular disease caused by expansions of a polyglutamine (polyQ) tract in the androgen receptor (AR) gene. SBMA is associated with the progressive loss of lower motor neurons, together with muscle weakness and atrophy. PolyQ-AR is converted to a toxic species upon binding to its natural ligands, testosterone, and dihydrotestosterone (DHT). Our previous patch-clamp studies on a motor neuron-derived cell model of SBMA showed alterations in voltage-gated ion currents. Here, we identified and characterized chloride currents most likely belonging to the chloride channel-2 (ClC-2) subfamily, which showed significantly increased amplitudes in the SBMA cells. The treatment with the pituitary adenylyl cyclase-activating polypeptide (PACAP), a neuropeptide with a proven protective effect in a mouse model of SBMA, recovered chloride channel current alterations in SBMA cells. These observations suggest that the CIC-2 currents are affected in SBMA, an alteration that may contribute and potentially determine the pathophysiology of the disease.

ClC-2-like Chloride Current Alterations in a Cell Model of Spinal and Bulbar Muscular Atrophy, a Polyglutamine Disease / Martinez-Rojas, V. A.; Jimenez-Garduno, A. M.; Michelatti, D.; Tosatto, L.; Marchioretto, M.; Arosio, D.; Basso, M.; Pennuto, M.; Musio, C.. - In: JOURNAL OF MOLECULAR NEUROSCIENCE. - ISSN 0895-8696. - 2020:(2020). [10.1007/s12031-020-01687-5]

ClC-2-like Chloride Current Alterations in a Cell Model of Spinal and Bulbar Muscular Atrophy, a Polyglutamine Disease

Michelatti D.;Tosatto L.;Marchioretto M.;Arosio D.;Basso M.;Pennuto M.;Musio C.
2020

Abstract

Spinal and bulbar muscular atrophy (SBMA) is a neuromuscular disease caused by expansions of a polyglutamine (polyQ) tract in the androgen receptor (AR) gene. SBMA is associated with the progressive loss of lower motor neurons, together with muscle weakness and atrophy. PolyQ-AR is converted to a toxic species upon binding to its natural ligands, testosterone, and dihydrotestosterone (DHT). Our previous patch-clamp studies on a motor neuron-derived cell model of SBMA showed alterations in voltage-gated ion currents. Here, we identified and characterized chloride currents most likely belonging to the chloride channel-2 (ClC-2) subfamily, which showed significantly increased amplitudes in the SBMA cells. The treatment with the pituitary adenylyl cyclase-activating polypeptide (PACAP), a neuropeptide with a proven protective effect in a mouse model of SBMA, recovered chloride channel current alterations in SBMA cells. These observations suggest that the CIC-2 currents are affected in SBMA, an alteration that may contribute and potentially determine the pathophysiology of the disease.
Martinez-Rojas, V. A.; Jimenez-Garduno, A. M.; Michelatti, D.; Tosatto, L.; Marchioretto, M.; Arosio, D.; Basso, M.; Pennuto, M.; Musio, C.
ClC-2-like Chloride Current Alterations in a Cell Model of Spinal and Bulbar Muscular Atrophy, a Polyglutamine Disease / Martinez-Rojas, V. A.; Jimenez-Garduno, A. M.; Michelatti, D.; Tosatto, L.; Marchioretto, M.; Arosio, D.; Basso, M.; Pennuto, M.; Musio, C.. - In: JOURNAL OF MOLECULAR NEUROSCIENCE. - ISSN 0895-8696. - 2020:(2020). [10.1007/s12031-020-01687-5]
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11572/284931
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