Arosio, D

Basso, M

Jim\ue9nez-Gardu\uf1o, Am

Marchioretto, M

Mart\uednez-Rojas, Va

Michelatti, D

Musio, C.

Pennuto, M

Tosatto, L

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

Martínez-Rojas VA

Jiménez-Garduño AM

Michelatti D

Tosatto L

Marchioretto M

Arosio D

Basso M

Pennuto M

Musio C.

Archivio istituzionale della ricerca - Università di Padova

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

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

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

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Archivio istituzionale della ricerca - Università di Padova