dc.contributor.author | Otero-Cruz, José David | |
dc.contributor.author | Báez-Pagán, Carlos Alberto | |
dc.contributor.author | Dorna-Pérez, Luisamari | |
dc.contributor.author | Grajales-Reyes, Gary Emanuel | |
dc.contributor.author | Ramírez-Ordoñez, Rosaura Teresa | |
dc.contributor.author | Luciano, Carlos A. | |
dc.contributor.author | Gómez, Christopher Manuel | |
dc.contributor.author | Lasalde-Dominicci, José A. | |
dc.date.accessioned | 2017-03-23T20:49:56Z | |
dc.date.available | 2017-03-23T20:49:56Z | |
dc.date.issued | 2010-08-27 | |
dc.identifier.citation | Otero-Cruz, José David et al. “Decoding Pathogenesis of Slow-Channel Congenital Myasthenic Syndromes Using Recombinant Expression and Mice Models.” Puerto Rico Health Sciences Journal 29.1 (2010): 4–17. | en_US |
dc.identifier.issn | 0738-0658 | |
dc.identifier.uri | http://hdl.handle.net/11721/1566 | |
dc.description.abstract | Despite the fact that they are orphan diseases, congenital myasthenic syndromes (CMS) challenge
those who suffer from it by causing fatigable muscle weakness, in the most benign cases, to a
progressive wasting of muscles that may sentence patients to a wheelchair or even death. Compared
to other more common neurological diseases, CMS are rare. Nevertheless, extensive research in CMS
is performed in laboratories such as ours. Among the diverse neuromuscular disorders of CMS, we
are focusing in the slow-channel congenital myasthenic syndrome (SCS), which is caused by
mutations in genes encoding acetylcholine receptor subunits. The study of SCS has evolved from
clinical electrophysiological studies to in vitro expression systems and transgenic mice models. The
present review evaluates the methodological approaches that are most commonly employed to assess
synaptic impairment in SCS and also provides perspectives for new approaches. Electrophysiological
methodologies typically employed by physicians to diagnose patients include electromyography,
whereas patient muscle samples are used for intracellular recordings, single-channel recordings and
toxin binding experiments. In vitro expression systems allow the study of a particular mutation
without the need of patient intervention. Indeed, in vitro expression systems have usually been
implicated in the development of therapeutic strategies such as quinidine- and fluoxetine-based
treatments and, more recently, RNA interference. A breakthrough in the study of SCS has been the
development of transgenic mice bearing the mutations that cause SCS. These transgenic mice models
have actually been key in the elucidation of the pathogenesis of the SCS mutations by linking IP-3
receptors to calcium overloading, as well as caspases and calpains to the hallmark of SCS, namely
endplate myopathy. Finally, we summarize our experiences with suspected SCS patients from a local
perspective and comment on one aspect of the contribution of our group in the study of SCS. | en_US |
dc.language.iso | en_US | en_US |
dc.publisher | Puerto Rico Health Sciences Journal | en_US |
dc.subject | Acetylcholine receptor | en_US |
dc.subject | congenital myasthenic syndromes | en_US |
dc.subject | slow-channel congenital myasthenic syndromes | en_US |
dc.title | Decoding Pathogenesis of Slow-Channel Congenital Myasthenic Syndromes using Recombinant Expression and Mice Models | en_US |
dc.type | Article | en_US |
dc.contributor.campus | University of Puerto Rico, Río Piedras Campus | |