We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Molecular mechanism of Spinocerebellar Ataxia type 6: glutamine repeat disorder, channelopathy and transcriptional dysregulation. The multifaceted aspects of a single mutation.
- Authors
Giunti, Paola; Mantuano, Elide; Frontali, Marina; Veneziano, Liana
- Abstract
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.
- Subjects
SPINOCEREBELLAR ataxia; POLYGLUTAMINE; GENETIC transcription; GENETIC mutation; PHENOTYPES; NEURONS
- Publication
Frontiers in Cellular Neuroscience, 2015, Vol 8/9, p1
- ISSN
1662-5102
- Publication type
Article
- DOI
10.3389/fncel.2015.00036