Molecular mechanism of Spinocerebellar Ataxia type 6:Glutamine repeat disorder,channelopathy and transcriptional dysregulation.The multifaceted aspects of a single mutation
| Autor: | Giunti P., Mantuano E., Frontali M., Veneziano L. |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: | |
| Zdroj: | Frontiers in cellular neuroscience 9 (2015). doi:10.3389/fncel.2015.00036 info:cnr-pdr/source/autori:Giunti P.; Mantuano E.; Frontali M.; Veneziano L./titolo:Molecular mechanism of Spinocerebellar Ataxia type 6:Glutamine repeat disorder,channelopathy and transcriptional dysregulation.The multifaceted aspects of a single mutation/doi:10.3389%2Ffncel.2015.00036/rivista:Frontiers in cellular neuroscience/anno:2015/pagina_da:/pagina_a:/intervallo_pagine:/volume:9 |
| DOI: | 10.3389/fncel.2015.00036 |
| Popis: | Spinocerebellar Ataxia type 6 (SCA6) is an autosomal dominant neurodegenerative disease characterized by late onset, slowly progressive, mostly pure cerebellar ataxia. It is one of three allelic disorders associated to CACNA1A gene, coding for the Alpha1 A subunit of P/Q type calcium channel Cav2.1 expressed in the brain, particularly in the cerebellum. The other two disorders are Episodic Ataxia type 2 (EA2), and Familial Hemiplegic Migraine type 1 (FHM1). These disorders show distinct phenotypes that often overlap but have different pathogenic mechanisms. EA2 and FHM1 are due to mutations causing, respectively, a loss and a gain of channel function. SCA6, instead, is associated with short expansions of a polyglutamine stretch located in the cytoplasmic C-terminal tail of the protein. This domain has a relevant role in channel regulation, as well as in transcription regulation of other neuronal genes; thus the SCA6 CAG repeat expansion results in complex pathogenic molecular mechanisms reflecting the complex Cav2.1 C-terminus activity. We will provide a short review for an update on the SCA6 molecular mechanism. |
| Databáze: | OpenAIRE |
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