ArticleActa neuropathologica2010
The carboxy-terminal fragment of alpha(1A) calcium channel preferentially aggregates in the cytoplasm of human spinocerebellar ataxia type 6 Purkinje cells.
Article in Acta neuropathologica, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 56 citations in OpenAlex.
- Redefining the Pathogenic CAG Repeat Units Threshold inNeurology. Genetics · 2025Article
- Progressive degeneration in a new Drosophila model of spinocerebellar ataxia type 7.Scientific reports · 2024Article
- Progressive degeneration in a newResearch square · 2023Article
- A neurodevelopmental disorder caused by a dysfunctionaleNeurologicalSci · 2023Article
- Cerebellar contribution to threat probability in a SCA6 mouse model.Human molecular genetics · 2022Article
- Calpain-mediated proteolysis as driver and modulator of polyglutamine toxicity.Frontiers in molecular neuroscience · 2022Review
- A survey of protein interactions and posttranslational modifications that influence the polyglutamine diseases.Frontiers in molecular neuroscience · 2022Review
- More than a pore: How voltage-gated calcium channels act on different levels of neuronal communication regulation.Channels (Austin, Tex.) · 2021Review
- Calcium Channel Splice Variants and Their Effects in Brain and Cardiovascular Function.Advances in experimental medicine and biology · 2021Article
- What is the Pathogenic CAG Expansion Length in Huntington's Disease?Journal of Huntington's disease · 2021Review
- Exploring the Potential of Small Molecule-Based Therapeutic Approaches for Targeting Trinucleotide Repeat Disorders.Molecular neurobiology · 2020Review
- Menthol evokes CaRedox biology · 2018Article
- Bicistronic CACNA1A Gene Expression in Neurons Derived from Spinocerebellar Ataxia Type 6 Patient-Induced Pluripotent Stem Cells.Stem cells and development · 2017Article
- Modulation of Molecular Chaperones in Huntington's Disease and Other Polyglutamine Disorders.Molecular neurobiology · 2017Review
- An miRNA-mediated therapy for SCA6 blocks IRES-driven translation of the CACNA1A second cistron.Science translational medicine · 2016Article
- Loss of MyD88 alters neuroinflammatory response and attenuates early Purkinje cell loss in a spinocerebellar ataxia type 6 mouse model.Human molecular genetics · 2015Article
- DNA/RNA heteroduplex oligonucleotide for highly efficient gene silencing.Nature communications · 2015Article
- DnaJ-1 and karyopherin α3 suppress degeneration in a new Drosophila model of Spinocerebellar Ataxia Type 6.Human molecular genetics · 2015Article
- Spinocerebellar ataxia type 6 protein aggregates cause deficits in motor learning and cerebellar plasticity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- Molecular mechanism of Spinocerebellar Ataxia type 6: glutamine repeat disorder, channelopathy and transcriptional dysregulation. The multifaceted aspects of a single mutation.Frontiers in cellular neuroscience · 2015Review
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Authors and funding
18 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Spinocerebellar ataxia type 6 (SCA6) is an autosomal dominant neurodegenerative disease caused by a small polyglutamine (polyQ) expansion (control: 4-20Q; SCA6: 20-33Q) in the carboxyl(C)-terminal cytoplasmic domain of the alpha(1A) voltage-dependent calcium channel (Ca(v)2.1). Although a 75-85-kDa Ca(v)2.1 C-terminal fragment (CTF) is toxic in cultured cells, its existence in human brains and its role in SCA6 pathogenesis remains unknown. Here, we investigated whether the small polyQ expansion alters the expression pattern and intracellular distribution of Ca(v)2.1 in human SCA6 brains. New antibodies against the Ca(v)2.1 C-terminus were used in immunoblotting and immunohistochemistry. In the cerebella of six control individuals, the CTF was detected in sucrose- and SDS-soluble cytosolic fractions; in the cerebella of two SCA6 patients, it was additionally detected in SDS-insoluble cytosolic and sucrose-soluble nuclear fractions. In contrast, however, the CTF was not detected either in the nuclear fraction or in the SDS-insoluble cytosolic fraction of SCA6 extracerebellar tissues, indicating that the CTF being insoluble in the cytoplasm or mislocalized to the nucleus only in the SCA6 cerebellum. Immunohistochemistry revealed abundant aggregates in cell bodies and dendrites of SCA6 Purkinje cells (seven patients) but not in controls (n = 6). Recombinant CTF with a small polyQ expansion (rCTF-Q28) aggregated in cultured PC12 cells, but neither rCTF-Q13 (normal-length polyQ) nor full-length Ca(v)2.1 with Q28 did. We conclude that SCA6 pathogenesis may be associated with the CTF, normally found in the cytoplasm, being aggregated in the cytoplasm and additionally distributed in the nucleus.
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