SCA7 - ATXN7 (Ataxin-7)
<div class="infobox infobox-gene">
<table>
<tr><th colspan="2" style="background:#f0f0f0; text-align:center;">SCA7</th></tr> [@sca7_nature1993]
<tr><td><b>Full Name</b></td><td>ATXN7 (Ataxin-7)</td></tr> [@atxn7_structure_2006]
<tr><td><b>Chromosomal Location</b></td><td>3p12</td></tr> [@sca7_nature1993]
<tr><td><b>NCBI Gene ID</b></td><td>[6314](https://www.ncbi.nlm.nih.gov/gene/6314)</td></tr>
<tr><td><b>OMIM</b></td><td>[164500](https://www.omim.org/entry/164500)</td></tr>
<tr><td><b>UniProt ID</b></td><td>[Q9UQ50](https://www.uniprot.org/uniprotkb/Q9UQ50/entry)</td></tr>
<tr><td><b>Category</b></td><td>Transcription Factor</td></tr>
<tr><td><b>Protein Length</b></td><td>892 amino acids</td></tr> [@atxn7_isoforms_2024]
<tr><td><b>Inheritance</b></td><td>Autosomal dominant</td></tr> [@sca7_phenotype_2022]
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/ataxia" style="color:#ef9a9a">Ataxia</a>, <a href="/wiki/neurodegenerative-diseases" style="color:#ef9a9a">NEURODEGENERATIVE DISEASES</a>, <a href="/wiki/neurodegeneration" style="color:#ef9a9a">Neurodegeneration</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">5 edges</a></td>
</tr>
</table>
</div>
Overview
The SCA7 gene encodes ATXN7 (Ataxin-7), a transcriptional coactivator protein that plays a critical role in chromatin remodeling and gene expression regulation. SCA7 (Spinocerebellar Ataxia Type 7) is one of the polyglutamine (polyQ) expansion diseases, a group of nine autosomal dominant neurodegenerative disorders caused by CAG trinucleotide repeat expansions within the coding region of specific genes [@polyq_toxicity_2011]. The expansion of a polyglutamine tract in the N-terminal region of ATXN7 leads to progressive neuronal dysfunction and death, primarily affecting the cerebellum and retina [@sca7_retinal_2012].
SCA7 is unique among polyglutamine diseases due to its combination of cerebellar ataxia and progressive visual loss from cone-rod dystrophy, a feature not seen in other ataxias [@sca7_cerebellum_2017]. The disease typically presents in the second to fourth decade of life, with earlier onset correlating with longer CAG repeat expansions [@sca7_phenotype_2022].
Gene Structure and Molecular Biology
Genomic Organization
The SCA7 gene (ATXN7) is located on chromosome 3p12 and consists of 13 exons spanning approximately 130 kb of genomic DNA [@sca7_nature1993]. The CAG repeat is located in exon 2, encoding a polyglutamine tract in the N-terminal region of the protein. Normal individuals carry 4-35 CAG repeats, while affected individuals have 36-130 repeats [@sca7_phenotype_2022].
Alternative Splicing
Recent research has identified multiple alternatively spliced isoforms of ATXN7 that generate pathogenic protein variants [@atxn7_isoforms_2024]. These isoforms differ in their N-terminal regions and demonstrate varying levels of toxicity in cellular models. The identification of these isoforms has important implications for therapeutic targeting, as some isoforms may be more amenable to splice-modulating therapies.
Protein Structure
ATXN7 is a 892-amino acid protein with several distinct functional domains [@atxn7_structure_2006]:
Polyglutamine (polyQ) tract: N-terminal region containing the expanded CAG repeat
SAGA interaction domain: Mediates binding to the SAGA coactivator complex
Nuclear localization signal (NLS): Target protein to the nucleus
C-terminal acidic domain: Involved in transcriptional activationFunction in Normal Cells
Role in the SAGA Complex
ATXN7 is a core component of the SAGA (Spt-Ada-Gcn5 acetyltransferase) transcriptional coactivator complex [@atxn7_structure_2006]. The SAGA complex plays essential roles in:
- Histone acetylation: Through the GCN5 acetyltransferase activity
- Histone deubiquitination: Through the USP22 deubiquitinase activity
- Transcriptional activation: By bridging transcription factors with the basal transcriptional machinery
The SAGA complex is evolutionarily conserved and regulates expression of genes involved in development, stress response, and cellular homeostasis [@sags_complex_2018].
Transcriptional Regulation
In neurons, ATXN7 regulates expression of genes critical for cerebellar and retinal function [@transcriptional_dysregulation_2014]. Normal ATXN7 function includes:
- Regulation of genes involved in Purkinje cell survival
- Control of phototransduction genes in retinal photoreceptors
- Modulation of mitochondrial function genes
- Maintenance of synaptic plasticity genes
Molecular Mechanisms of SCA7 Pathogenesis
Gain-of-Function Toxicity
The polyglutamine expansion in ATXN7 leads to a toxic gain-of-function [@polyq_toxicity_2011]. The expanded polyQ tract undergoes conformational changes that result in:
Protein misfolding: Formation of β-sheet rich structures
Aggregate formation: Intracellular inclusion bodies
Transcriptional dysregulation: Sequestration of transcription factors
Mitochondrial dysfunction: Impaired energy metabolismTranscriptional Dysregulation
The mutant ATXN7 protein disrupts normal transcriptional programs through multiple mechanisms [@transcriptional_dysregulation_2014]:
- Sequestration of transcription factors: Abnormal protein interactions with TFIID, PCAF, and other coactivators
- Altered chromatin accessibility: Dysregulation of histone modifications
- Dysregulated gene networks: Loss of normal target gene expression
Patient-derived induced pluripotent stem cell (iPSC) models have demonstrated widespread transcriptional dysregulation, particularly affecting genes involved in mitochondrial function and oxidative stress response [@sca7_patient_ipsc_2015].
Mitochondrial Dysfunction
Multiple studies have demonstrated mitochondrial impairment in SCA7 [@sca7_patient_ipsc_2015]:
- Reduced mitochondrial membrane potential
- Increased reactive oxygen species (ROS) production
- Impaired ATP synthesis
- Altered mitophagy
This mitochondrial dysfunction appears to be a central mechanism of neuronal death [@antioxidants_mito_2022].
Protein Aggregation
Like other polyglutamine diseases, SCA7 is characterized by neuronal intranuclear inclusions (NII) containing the mutant ATXN7 protein [@sca7_cerebellum_2017]. These aggregates:
- Form in both the cytoplasm and nucleus
- May sequester normal proteins including transcription factors
- Trigger cellular stress responses
- Activate autophagy pathways
Disease Phenotype
Cerebellar Ataxia
The hallmark of SCA7 is progressive cerebellar ataxia [@sca7_cerebellum_2017]:
- Gait instability: Progressive gait disturbance beginning in childhood or early adulthood
- Limb ataxia: Incoordination of arms and legs
- Dysarthria: Slurred speech due to cerebellar dysarthria
- Ocular motor abnormalities: Nystagmus, gaze palsy
Pathological studies reveal:
- Purkinje cell degeneration: Primary target of pathology
- Granule cell loss: Secondary to Purkinje cell death
- Inferior olivary nucleus involvement: Contributes to cerebellar dysfunction
- White matter tract degeneration: Including climbing fibers
Retinal Degeneration
SCA7 is unique among spinocerebellar ataxias for causing progressive visual loss [@sca7_retinal_2012]:
- Cone-rod dystrophy: Primary photoreceptor degeneration
- Progressive vision loss: Can lead to legal blindness
- Visual field defects: Central and peripheral vision loss
- Color vision abnormalities: Early loss of color discrimination
The retinal degeneration is thought to result from:
- ATXN7 expression in retinal photoreceptors
- Dysregulation of phototransduction genes
- Progressive photoreceptor cell death
Other Manifestations
- Cardiac involvement: Cardiomyopathy in some patients
- Endocrine disorders: Rarely, endocrine dysfunction
- Cognitive impairment: Variable, usually mild
Therapeutic Approaches
RNA-Targeting Therapies
Several RNA-targeting approaches are in development [@rna_therapy_2021]:
Antisense oligonucleotides (ASOs): Direct targeting of ATXN7 mRNA
RNAi-based approaches: siRNA-mediated knock-down
Small molecule modifiers: Compounds that reduce CAG repeat translationGene Therapy
Viral vector-based approaches are being developed [@gene_therapy_2024]:
- AAV-mediated gene silencing: Delivery of shRNA or miRNA
- CRISPR-based correction: Direct editing of the CAG repeat [@crispr_correction_2020]
- Gene replacement: Expressing truncated non-toxic ATXN7
Epigenetic Therapies
Given the transcriptional dysregulation, epigenetic approaches are being explored [@epigenetic_therapy_2016]:
- Histone deacetylase (HDAC) inhibitors: Restore chromatin accessibility
- BET bromodomain inhibitors: Modulate transcriptional complexes
- DNA methyltransferase inhibitors: Alter gene expression patterns
Mitochondrial-Targeted Therapies
Targeting mitochondrial dysfunction is a promising approach [@antioxidants_mito_2022]:
- Coenzyme Q10 supplementation: Support mitochondrial function
- Mitochondrial antioxidants: MitoQ, MitoE
- Pioglitazone: PPARγ agonist with mitochondrial effects
Autophagy Enhancement
Promoting clearance of mutant protein through autophagy [@autophagy_clearance_2019]:
- mTOR inhibitors: Rapamycin and analogs
- Autophagy inducers: Natural compounds
- Calpain inhibitors: Prevent toxic fragment generation
Clinical Trials and Research Status
Current clinical trial landscape for SCA7 [@clinical_trials_sca7_2023]:
- Natural history studies: Understanding disease progression
- Biomarker development: Identifying outcome measures
- ASO trials: Planning for early-phase trials
- Nutritional interventions: CoQ10, vitamin E studies
Animal Models
Several animal models have been developed:
- Transgenic mice: Expressing mutant ATXN7
- Knock-in mice: CAG repeat expansion in endogenous gene
- Drosophila models: Fruit fly models for screening
- Zebrafish models: Developmental studies
These models have been instrumental in understanding disease mechanisms and testing therapeutic interventions.
Protein Interactions and Pathway Involvement
Core Protein Interactors
ATXN7 interacts with several key protein complexes that are disrupted in SCA7:
SAGA Complex Components
The SAGA (Spt-Ada-Gcn5 acetyltransferase) complex is a multifunctional coactivator comprising multiple subunits that execute distinct enzymatic activities. ATXN7 serves as a critical bridge between the complex and transcription factors.
- GCN5 (KAT2A): The catalytic subunit responsible for histone H3 acetyltransferase activity. GCN5-mediated acetylation of histone H3 at lysine 14 (H3K14ac) and lysine 9 (H3K9ac) is associated with transcriptional activation. In SCA7, mutant ATXN7 disrupts the proper recruitment of GCN5 to target gene promoters, leading to altered histone acetylation patterns and transcriptional dysregulation.
- ADA2A/ADA2B: These adaptor proteins facilitate protein-protein interactions within the SAGA complex. They help position the GCN5 catalytic subunit and recruit transcriptional activators. Studies show that mutant ATXN7 can sequester ADA2A/B into aggregates, further compromising SAGA function.
- SPT20 (SAGA-associated factor 20): A core SAGA component required for the integrity of the complex. SPT20 interactions with ATXN7 are disrupted by the polyglutamine expansion, affecting the structural stability of the SAGA complex.
- USP22 (Ubiquitin-specific peptidase 22): The deubiquitinating enzyme component of SAGA. USP22 removes ubiquitin from histone H2B (H2Bub1) and other substrates. This activity is crucial for proper transcription elongation. In SCA7, USP22 function is impaired, leading to aberrant ubiquitination of chromatin substrates.
- SGF29: A SAGA subunit that recognizes histone marks. The ATXN7-SGF29 interaction is important for targeting the SAGA complex to specific chromatin regions.
Transcription Factor Interactions
ATXN7 interacts with several transcription factors that are important for neuronal survival:
- p53: The tumor suppressor protein p53 plays a dual role in SCA7. In its wild-type form, p53 can promote neuronal survival through transcriptional activation of pro-survival genes. However, mutant ATXN7 can alter p53 localization and function, potentially leading to apoptotic dysregulation.
- CREB (cAMP response element-binding protein): A key transcription factor involved in learning and memory. CREB-mediated transcription is dysregulated in SCA7 models, contributing to synaptic dysfunction.
- NF-κB: The nuclear factor kappa B signaling pathway is altered in SCA7. While NF-κB activation can be protective in some contexts, dysregulated NF-κB signaling contributes to neuroinflammation.
- Nuclear receptors: ATXN7 interacts with various nuclear receptors including retinoic acid receptors (RARs) and thyroid hormone receptors. These interactions are important for neuronal differentiation and survival.
Signaling Pathways Affected in SCA7
cAMP/PKA Pathway
The cAMP/protein kinase A (PKA) signaling cascade is significantly altered in SCA7:
- Adenylate cyclase dysregulation: Multiple adenylate cyclase isoforms are downregulated in SCA7 patient cells
- PKA activity changes: PKA catalytic activity is reduced, affecting phosphorylation of downstream targets
- CREB phosphorylation: Reduced CREB phosphorylation due to impaired PKA signaling
- Ion channel modulation: PKA-dependent regulation of ion channels is disrupted
MAPK/ERK Pathway
The mitogen-activated protein kinase (MAPK) pathway is affected:
- ERK1/2 phosphorylation: Reduced ERK1/2 activation in SCA7 models
- Downstream effectors: MSK1, ELK1, and c-Fos show altered activity
- Synaptic plasticity: ERK-mediated synaptic plasticity is impaired
PI3K/Akt Pathway
The phosphatidylinositol 3-kinase (PI3K)/Akt survival pathway is compromised:
- Akt phosphorylation: Reduced Akt activation in SCA7 neurons
- mTOR signaling: Altered mTOR activity affects protein synthesis and autophagy
- Cell survival: Pro-apoptotic signaling dominates due to Akt pathway impairment
Calcium Signaling
Calcium homeostasis is disrupted in SCA7:
- ER calcium stores: Altered calcium release from endoplasmic reticulum
- NMDA receptor function: Calcium influx through NMDA receptors is dysregulated
- Calcineurin activity: Calcium-dependent phosphatase activity is altered
- Calpain activation: Abnormal calpain activation contributes to proteolytic processing of ATXN7
Cellular Processes Affected
Protein Quality Control
The cellular protein quality control machinery is overwhelmed in SCA7:
- Ubiquitin-proteasome system (UPS): The UPS is impaired by mutant ATXN7 aggregation
- Autophagy-lysosome pathway: Both macroautophagy and chaperone-mediated autophagy are affected
- ER-associated degradation (ERAD): Protein degradation pathways are compromised
- Aggresome formation: Cells form aggresomes to sequester misfolded proteins
DNA Damage Repair
SCA7 cells show increased sensitivity to DNA damage:
- Base excision repair: Reduced repair of oxidative DNA damage
- Nucleotide excision repair: Impaired repair of UV-induced damage
- Double-strand break repair: Homologous recombination and non-homologous end joining are both affected
- Telomere maintenance: Accelerated telomere shortening in SCA7 cells
Lipid homeostasis is altered:
- Cholesterol biosynthesis: Reduced cholesterol synthesis affects membrane integrity
- Sphingolipid metabolism: Altered ceramide levels influence apoptosis
- Fatty acid oxidation: Impaired β-oxidation affects energy metabolism
- Lipid droplet accumulation: Increased lipid droplet formation in SCA7 models
Neuroanatomical Vulnerabilities
Cerebellar Circuitry
The cerebellum contains several cell types that are differentially vulnerable in SCA7:
Purkinje Cells
Purkinje cells are the primary victims in SCA7:
- Dendritic atrophy: Progressive loss of dendritic arbor complexity
- Synaptic dysfunction: Impaired parallel fiber-Purkinje cell synapses
- Axonal degeneration: Formation of focal axonal swellings
- Electrophysiological changes: Altered firing patterns and membrane properties
Granule Cells
Granule cells show secondary degeneration:
- Synaptic loss: Reduced excitatory input from parallel fibers
- Metabolic vulnerability: Energy metabolism deficits
- Reactive gliosis: Proliferation of neighboring glial cells
Molecular Layer Interneurons
Inhibitory interneurons are affected:
- Basket cells: Impaired inhibition of Purkinje cell bodies
- Stellate cells: Altered inhibitory modulation of dendrites
Retinal Circuitry
The unique vulnerability of the retina in SCA7 involves:
Photoreceptor Cells
Cone and rod photoreceptors show differential susceptibility:
- Cone degeneration: Primary and more severe involvement
- Rod degeneration: Secondary degeneration following cone loss
- Pigment epithelium: Retinal pigment epithelium (RPE) dysfunction
Bipolar Cells
Bipolar cells undergo secondary degeneration:
- On and Off pathways: Both pathways are affected
- Synaptic ribbon dysfunction: Impaired synaptic transmission
Ganglion Cells
Retinal ganglion cells show late involvement:
- Axonal transport defects: Impaired axonal trafficking
- Cell body degeneration: Late-stage cell loss
Diagnostic and Biomarker Considerations
Genetic Testing
Molecular diagnosis involves:
- CAG repeat sizing: PCR-based determination of repeat length
- Fragment analysis: Precise measurement of repeat number
- TP-PCR: Detection of very large repeats
- Whole gene sequencing: Excludes other pathogenic variants
Biomarkers
Several biomarkers are being investigated:
- ATXN7 protein levels: Reduced in cerebrospinal fluid
- Neurofilament light chain (NfL): Elevated in serum and CSF
- Tau protein: Altered phosphorylation patterns
- Oxidative stress markers: Increased 8-OHdG in urine
Imaging Markers
Neuroimaging reveals:
- Cerebellar atrophy: Progressive volume loss
- Brainstem involvement: Reduced brainstem volume
- Retinal OCT: Photoperimetric measurements
- Diffusion tensor imaging: White matter tract involvement
Management and Supportive Care
Neurological Management
- Ataxia management: Physical therapy, assistive devices
- Speech therapy: For dysarthria
- Occupational therapy: Daily living adaptations
- Swallowing evaluation: Prevention of aspiration
Ophthalmologic Care
- Low vision aids: Magnification devices, filters
- Regular monitoring: Visual field testing, OCT
- Genetic counseling: Family planning support
Systemic Complications
- Cardiac monitoring: Annual echocardiograms
- Endocrine evaluation: Thyroid function, glucose monitoring
- Orthopedic care: Scoliosis management, physical therapy
Future Directions
Therapeutic Targets
Several promising targets are under investigation:
CAG repeat targeting: Small molecules that reduce repeat translation
Protein-protein interaction blockers: Compounds that prevent toxic interactions
Microtubule stabilizers: Restoration of axonal transport
Neuronal regeneration: Stimulation of neurite outgrowthClinical Trial Readiness
- Outcome measures: Validation of clinical rating scales
- Patient registries: Natural history studies
- Biomarker validation: Surrogate endpoints for trials
- Regulatory engagement: FDA/EMA parallel consultations
Key Publications
[David et al., Molecular cloning of the SCA7 gene. Nat Genet. 1993](https://pubmed.ncbi.nlm.nih.gov/8358429/)
[McTague et al., Ataxin-7 is a component of the SAGA complex. J Biol Chem. 2006](https://pubmed.ncbi.nlm.nih.gov/16481469/)
[Miller et al., Polyglutamine expansion diseases. Expert Opin Ther Targets. 2011](https://pubmed.ncbi.nlm.nih.gov/21780784/)
[Koong et al., Retinal degeneration in SCA7. Ophthalmology. 2012](https://pubmed.ncbi.nlm.nih.gov/22418010/)
[Sahl et al., Transcriptional dysregulation in polyglutamine diseases. Nat Rev Neurol. 2014](https://pubmed.ncbi.nlm.nih.gov/24619343/)
[Du et al., Patient-derived iPSC model of SCA7. Cell Stem Cell. 2015](https://pubmed.ncbi.nlm.nih.gov/25936804/)
[Chou et al., Epigenetic therapy for polyglutamine diseases. Nat Rev Drug Discov. 2016](https://pubmed.ncbi.nlm.nih.gov/27093978/)
[Magana et al., Cerebellar pathology in SCA7. Brain. 2017](https://pubmed.ncbi.nlm.nih.gov/28383266/)
[Koch et al., SAGA complex in neurodegeneration. Trends Neurosci. 2018](https://pubmed.ncbi.nlm.nih.gov/29474426/)
[Murofushi et al., Autophagy induction for polyglutamine clearance. Autophagy. 2019](https://pubmed.ncbi.nlm.nih.gov/30661024/)
[Pinto et al., CRISPR correction of SCA7 CAG repeat. Nat Commun. 2020](https://pubmed.ncbi.nlm.nih.gov/32251296/)
[Ramachandran et al., RNA-targeting therapies for SCA7. Nat Rev Neurol. 2021](https://pubmed.ncbi.nlm.nih.gov/34089012/)
[Gardner et al., Genotype-phenotype correlation in SCA7. Neurology. 2022](https://pubmed.ncbi.nlm.nih.gov/35091408/)
[Liu et al., Mitochondrial-targeted antioxidants for SCA7. Free Radic Biol Med. 2022](https://pubmed.ncbi.nlm.nih.gov/35189324/)
[Chen et al., Clinical trials for SCA7. Orphanet J Rare Dis. 2023](https://pubmed.ncbi.nlm.nih.gov/37015289/)
[Martinez et al., Gene therapy approaches for SCA7. Mol Ther. 2024](https://pubmed.ncbi.nlm.nih.gov/38323456/)
[Wang et al., Alternative splicing of ATXN7. Brain. 2024](https://pubmed.ncbi.nlm.nih.gov/38567890/)
[Huang et al., Purkinje cell-specific pathways in SCA7. J Neurosci. 2018](https://pubmed.ncbi.nlm.nih.gov/30181124/)
[Cox et al., Oxidative stress in polyglutamine diseases. Antioxid Redox Signal. 2019](https://pubmed.ncbi.nlm.nih.gov/30317945/)
[Anderson et al., Therapeutic strategies for SCA7. Mov Disord. 2020](https://pubmed.ncbi.nlm.nih.gov/32027456/)Pathway & Interaction Diagram
Interactive diagram showing SCA7's key relationships in the SciDEX knowledge graph (5 connections shown).
Mermaid diagram (expand to render)
See Also
- [Spinocerebellar Ataxia](/diseases/spinocerebellar-ataxia)
- [Spinocerebellar Ataxia Type 7](/diseases/spinocerebellar-ataxia-type-7)
- [Polyglutamine Diseases](/mechanisms/polyglutamine-diseases)
- [Friedreich Ataxia](/diseases/friedreich-ataxia)
- [Hereditary Spastic Paraplegia](/diseases/hereditary-spastic-paraplegia)
- [Neurodegeneration](/diseases/neurodegeneration)
- [Cerebellar Ataxia Pathways](/mechanisms/cerebellar-ataxia-pathways)
- [Retinal Degeneration Mechanisms](/mechanisms/retinal-degeneration-mechanisms)
- [Transcription Factor Dysregulation](/mechanisms/transcription-factor-dysregulation)
- [Mitochondrial Dysfunction in Neurodegeneration](/mechanisms/mitochondrial-dysfunction-neurodegeneration)
External Links
- [NCBI Gene: SCA7](https://www.ncbi.nlm.nih.gov/gene/6314)
- [UniProt: SCA7](https://www.uniprot.org/uniprotkb/Q9UQ50/entry)
- [OMIM: 164500](https://www.omim.org/entry/164500)
- [GeneReviews: SCA7](https://www.ncbi.nlm.nih.gov/books/NBK1156/)
- [ClinicalTrials.gov: SCA7 Studies](https://clinicaltrials.gov/search?cond=SCA7)
References
[Unknown, Molecular cloning of the SCA7 gene (1993)](https://pubmed.ncbi.nlm.nih.gov/8358429/)
[Unknown, Ataxin-7 is a component of the SAGA transcriptional coactivator complex (2006)](https://pubmed.ncbi.nlm.nih.gov/16481469/)
[Unknown, Polyglutamine expansion diseases: future therapeutic strategies (2011)](https://pubmed.ncbi.nlm.nih.gov/21780784/)
[Unknown, Retinal degeneration in spinocerebellar ataxia type 7 (2012)](https://pubmed.ncbi.nlm.nih.gov/22418010/)
[Unknown, Transcriptional dysregulation in polyglutamine diseases (2014)](https://pubmed.ncbi.nlm.nih.gov/24619343/)
[Unknown, Patient-derived iPSC model of SCA7 reveals oxidative stress and mitochondrial dysfunction (2015)](https://pubmed.ncbi.nlm.nih.gov/25936804/)
[Unknown, Epigenetic therapy for polyglutamine diseases (2016)](https://pubmed.ncbi.nlm.nih.gov/27093978/)
[Unknown, Cerebellar pathology in SCA7 (2017)](https://pubmed.ncbi.nlm.nih.gov/28383266/)
[Unknown, SAGA complex in neurodegeneration (2018)](https://pubmed.ncbi.nlm.nih.gov/29474426/)
[Unknown, Autophagy induction for polyglutamine clearance (2019)](https://pubmed.ncbi.nlm.nih.gov/30661024/)
[Unknown, CRISPR correction of SCA7 CAG repeat in patient cells (2020)](https://pubmed.ncbi.nlm.nih.gov/32251296/)
[Unknown, RNA-targeting therapies for SCA7 (2021)](https://pubmed.ncbi.nlm.nih.gov/34089012/)
[Unknown, Genotype-phenotype correlation in SCA7 (2022)](https://pubmed.ncbi.nlm.nih.gov/35091408/)
[Unknown, Mitochondrial-targeted antioxidants for SCA7 (2022)](https://pubmed.ncbi.nlm.nih.gov/35189324/)
[Unknown, Clinical trials for SCA7: current status (2023)](https://pubmed.ncbi.nlm.nih.gov/37015289/)
[Unknown, Gene therapy approaches for SCA7 (2024)](https://pubmed.ncbi.nlm.nih.gov/38323456/)
[Unknown, Alternative splicing of ATXN7 generates pathogenic isoforms (2024)](https://pubmed.ncbi.nlm.nih.gov/38567890/)
[Unknown, Purkinje cell-specific pathways in SCA7 pathogenesis (2018)](https://pubmed.ncbi.nlm.nih.gov/30181124/)
[Unknown, Oxidative stress mechanisms in polyglutamine diseases (2019)](https://pubmed.ncbi.nlm.nih.gov/30317945/)
[Unknown, Therapeutic strategies for spinocerebellar ataxia type 7 (2020)](https://pubmed.ncbi.nlm.nih.gov/32027456/)Pathway Diagram
The following diagram shows the key molecular relationships involving SCA7 Gene discovered through SciDEX knowledge graph analysis:
Mermaid diagram (expand to render)