A doença de Machado-Joseph tipo 1 é um subtipo raro e geralmente grave da doença de Machado-Joseph (também conhecida como SCA3/MJD), caracterizada pela presença de sinais neurológicos marcantes que afetam o controle dos movimentos e a coordenação muscular.
Introdução
O que você precisa saber de cara
A doença de Machado-Joseph tipo 1 é um subtipo raro e geralmente grave da doença de Machado-Joseph (também conhecida como SCA3/MJD), caracterizada pela presença de sinais neurológicos marcantes que afetam o controle dos movimentos e a coordenação muscular.
Escala de raridade
<1/50kMuito rara
1/20kRara
1/10kPouco freq.
1/5kIncomum
1/2k
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Sinais e sintomas
O que aparece no corpo e com que frequência cada sintoma acontece
Partes do corpo afetadas
+ 15 sintomas em outras categorias
Características mais comuns
Os sintomas variam de pessoa para pessoa. Abaixo estão as 34 características clínicas mais associadas, ordenadas por frequência.
Linha do tempo da pesquisa
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Genética e causas
O que está alterado no DNA e como passa nas famílias
Genes associados
1 gene identificado com associação a esta condição. Padrão de herança: Autosomal dominant.
Deubiquitinating enzyme involved in protein homeostasis maintenance, transcription, cytoskeleton regulation, myogenesis and degradation of misfolded chaperone substrates (PubMed:12297501, PubMed:16118278, PubMed:17696782, PubMed:23625928, PubMed:28445460, PubMed:33157014). Binds long polyubiquitin chains and trims them, while it has weak or no activity against chains of 4 or less ubiquitins (PubMed:17696782). Involved in degradation of misfolded chaperone substrates via its interaction with STUB
Nucleus matrixNucleusLysosome membrane
Spinocerebellar ataxia 3
Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to cerebellum degeneration with variable involvement of the brainstem and spinal cord. SCA3 belongs to the autosomal dominant cerebellar ataxias type I (ADCA I) which are characterized by cerebellar ataxia in combination with additional clinical features like optic atrophy, ophthalmoplegia, bulbar and extrapyramidal signs, peripheral neuropathy and dementia. The molecular defect in SCA3 is the a CAG repeat expansion in ATX3 coding region. Longer expansions result in earlier onset and more severe clinical manifestations of the disease.
Variantes genéticas (ClinVar)
31 variantes patogênicas registradas no ClinVar.
Vias biológicas (Reactome)
2 vias biológicas associadas aos genes desta condição.
Diagnóstico
Os sinais que médicos procuram e os exames que confirmam
Tratamento e manejo
Remédios, cuidados de apoio e o que precisa acompanhar
Onde tratar no SUS
Hospitais de referência no Brasil e o protocolo oficial do SUS (PCDT)
🇧🇷 Atendimento SUS — Doença de Machado–Joseph, tipo 1
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Publicações mais relevantes
Gastrodin inhibits the formation of ataxin-3 aggregates by regulating the level of ERK1/2/P38 proteins.
Spinocerebellar ataxia type 3 (SCA3/Machado-Joseph disease), an incurable autosomal dominant neurodegenerative disorder, is caused by cytotoxic aggregation of polyglutamine-expanded ataxin-3 protein. Novel therapeutic strategies targeting its pathogenesis are urgently needed. Given gastrodin’s established antioxidative and neuroprotective properties, this study investigated its therapeutic potential against SCA3 pathogenesis. Three distinct cell models including parental HEK293T, ataxin-3-15Q (physiologic), and ataxin-3-77Q (pathogenic) were employed to assess gastrodin cytotoxicity, quantify insoluble aggregate formation and measure soluble ataxin-3 levels. Mechanistic studies included antioxidant capacity assays, human phosphokinase array profiling (37 kinases) and western blot validation of MAPK pathway components. Gastrodin treatment showed no cytotoxicity, significantly suppressed ataxin-3-77Q aggregate accumulation (p < 0.01), increased soluble ataxin-3 levels, enhanced cellular antioxidant capacity and selectively downregulated ERK1/2 and p38 proteins in MAPK pathways. We provide first evidence that gastrodin mitigates polyQ-mediated proteotoxicity by reducing ataxin-3 aggregation through suppression of the ERK1/2-p38 signaling axis in cellular models, revealing a novel mechanistic basis for SCA3 therapeutic development. The online version contains supplementary material available at 10.1186/s13023-025-04089-1. Gastrodin’s safety profile was demonstrated in SCA3 cellular models at concentrations up to 100 µM without causing cytotoxicity. Gastrodin significantly reduced the formation of polyQ-expanded ataxin-3 aggregates. There was a dose-dependent increase in soluble ataxin-3 levels by gastrodin. Gastrodin was found to attenuate SCA3 proteotoxicity in cellular models by simultaneously decreasing the total protein levels of ERK1/2 and p38. The online version contains supplementary material available at 10.1186/s13023-025-04089-1.
Peripheral and autonomic nervous system involvement in spinocerebellar ataxia type 3: unveiling an invisible burden.
Neuropathological examinations in spinocerebellar ataxia type 3 (SCA3) have demonstrated peripheral and autonomic nervous system degeneration, but the impact of associated symptoms on genetically affected individuals at different disease stages remains understudied. To investigate the clinical burden of peripheral and autonomic nervous system involvement in SCA3 mutation carriers across the disease spectrum. Forty SCA3 mutation carriers, including ten pre-ataxic individuals, completed questionnaires about muscle cramps, neuropathic pain, autonomic symptoms, activities of daily living, and quality of life, and underwent a standardized clinical examination of ataxia and neuropathy severity. Data were compared with 16 healthy controls. All but one of the ataxic and 60% of pre-ataxic individuals experienced muscle cramps at least weekly. Neuropathic pain was reported by 20% of pre-ataxic and 16.7% of ataxic mutation carriers, while the average number of autonomic symptoms in both groups was 2 and 4.7, respectively. Neuropathy severity scores were significantly higher in pre-ataxic and ataxic individuals than in healthy controls and associated with (i) worse self-reported functional status and (ii) clinician-reported ataxia severity. The number of autonomic symptoms was associated with patient-reported impairments in daily life and quality of life. Clinical features of peripheral and autonomic nervous system degeneration are very common in SCA3, may already be observed in pre-ataxic individuals, and independently contribute to patient-reported disease burden and clinician-rated overall ataxia severity.
Investigating the pathogenic role of calpain proteases and the therapeutic potential of their inhibition in mice modelling Machado-Joseph disease.
Machado-Joseph disease (MJD, also known as spinocerebellar ataxia type-3) is a fatal disease characterised by motor impairments and the presence of aggregated ataxin-3, the protein affected in MJD, in degenerating brain regions. Ataxin-3 protein aggregates have previously been reported to contain both full-length ataxin-3 protein and shorter protein fragments, highlighting proteolytic cleavage as a pathogenic mechanism. Calpains, calcium-activated proteases, have been reported to cleave ataxin-3 and have been implicated in MJD pathogenesis. This study aimed to explore whether calpain proteases were overactive at early, pathogenesis-relevant timepoints in male transgenic CMVMJD135 mice modelling MJD and identify the timepoint of calpain overactivation through obtaining longitudinal plasma samples. We detected increased levels of cleaved αII-spectrin in plasma from MJD mice as early as 12 weeks of age, shortly after the onset of neurological symptoms. Cerebellar and brainstem tissue from 15-week-old mice was immunoblotted, revealing a trend towards increased levels of calpain 1, and increased cleavage of calpain substrates such as αII-spectrin, beclin-1 and TAR DNA binding protein 43 (TDP-43) within the cerebellum. Further, we found that short-term treatment of male MJD mice (from 10 to 12 weeks of age) with the calpain inhibitor compound calpeptin yielded improvements in neurological symptoms and reduced the presence of cleaved αII-spectrin in plasma and cerebellum tissue when compared to vehicle treated MJD males. Our findings suggest that calpain overactivity may be an early disease phenotype that contributes to neurodegeneration in transgenic CMVMJD135 mice modelling MJD, and that calpeptin warrants further investigation as a potential treatment for MJD.
Extracellular vesicles-associated AAVs for the treatment of Machado-Joseph disease.
Machado-Joseph disease (MJD) is the most common dominant autosomal inherited ataxia worldwide, caused by the overrepetition of the trinucleotide CAG in the ATXN3 gene. This leads to the accumulation of mutant ataxin-3 protein and neurodegeneration. Currently, treatment remains symptomatic, although gene therapy has emerged as a promising approach. However, efficient and minimally invasive gene delivery to the brain remains a challenge. Extracellular vesicle-associated adeno-associated virus (EV-AAV) vectors are a novel delivery system, combining the ability of AAV vectors to deliver genes with the capacity of extracellular vesicles to bypass the immune system and cross the blood-brain barrier (BBB). Previous studies, however, have only combined AAV serotypes known to efficiently cross the BBB with EVs as a non-invasive delivery system to the brain. Thus, the ability of EV-AAVs to cross the BBB remained inconclusive. In this study, we evaluated whether AAV1/2 serotype, combined with rabies virus glycoprotein (RVg)-coated EVs, could effectively target the brain. Two isolation methods, differential ultracentrifugation and size-exclusion chromatography (SEC) were compared, with SEC yielding higher EV recovery. Moreover, RVg-EV-AAV1/2 successfully crossed the BBB and transduced mouse brains, leading to motor and neuropathologic improvements in an MJD mouse model. This study demonstrates that RVg-EV-AAVs are promising non-invasive delivery systems for MJD gene therapy.
IGFBP1 as a metabolic-neurodegenerative biomarker in spinocerebellar ataxia type 3.
Spinocerebellar ataxia type 3 (SCA3) is a progressive neurodegenerative disorder for which reliable metabolic biomarkers are lacking. Insulin-like growth factor binding protein 1 (IGFBP1), a stress-responsive protein regulated by insulin signaling, serves as an indicator of neurodegenerative burden. The present study aimed to measure the plasma levels of insulin, glucose, IGF1, IGF2, IGFBP1, IGFBP3 and neurofilament light chain (NfL) in patients with genetically confirmed SCA3 and age-matched controls. In addition, the association between the above molecules and clinical severity were assessed using the scale for the Assessment and Rating of Ataxia score, body mass index (BMI) and NfL levels, whereas metabolic-neurodegenerative interactions were assessed by stratifying patients by insulin tertiles. A total of 32 individuals with SCA3 and 36 age- and sex-matched controls were enrolled in the current study. The results demonstrated that patients with SCA3 exhibited markedly elevated IGFBP1, IGF2 and free IGF1 levels, as well as reduced insulin and higher glucose-to-insulin ratios, thus indicating disrupted insulin signaling. IGFBP1 was positively associated with SARA score and NfL levels and negatively associated with BMI. Notably, patients in the lowest insulin tertile (<3.65 µIU/ml) showed significantly higher IGFBP1 and NfL levels compared with the remaining groups, thus suggesting that the insulin/IGFBP1/NfL axis was associated with ataxia severity. Collectively, IGFBP1 could be a promising peripheral biomarker reflecting both metabolic and neurodegenerative processes in SCA3 and could facilitate monitoring of disease stages.
Publicações recentes
Extracellular vesicles-mediated delivery of SpCas9 RNPs for therapeutic gene editing in Spinocerebellar Ataxia Type 3.
Revisited case for intranasal neuropeptide Y based therapeutics: From preclinical to clinical.
Retrotransposition Events Shape the Evolution of the Ataxin-3 Gene Family in Primates.
IGFBP1 as a metabolic-neurodegenerative biomarker in spinocerebellar ataxia type 3.
Gastrodin inhibits the formation of ataxin-3 aggregates by regulating the level of ERK1/2/P38 proteins.
📚 EuropePMC582 artigos no totalmostrando 199
IGFBP1 as a metabolic-neurodegenerative biomarker in spinocerebellar ataxia type 3.
Experimental and therapeutic medicineGastrodin inhibits the formation of ataxin-3 aggregates by regulating the level of ERK1/2/P38 proteins.
Orphanet journal of rare diseasesSingle-Cell RNA Sequencing Reveals Impaired CHIP-Mediated Heat Stress Response in SCA3 Pathogenesis.
Molecular neurobiologyRepurposing of natural products for spinocerebellar ataxia type 3 using integrated network pharmacology and in silico approaches.
Scientific reportsPeripheral and autonomic nervous system involvement in spinocerebellar ataxia type 3: unveiling an invisible burden.
Journal of neurologyInvestigating the pathogenic role of calpain proteases and the therapeutic potential of their inhibition in mice modelling Machado-Joseph disease.
Human molecular geneticsBrain atrophy staging in spinocerebellar ataxia type 3 for clinical prognosis and trial enrichment.
EBioMedicineRegional brain atrophy subtypes in spinocerebellar ataxia type 3: links to clinical performance and treatment response.
Journal of neurologyManaging symptoms and improving the quality of life of persons with Machado-Joseph disease.
Expert review of neurotherapeuticsPragmatic Feasibility Study Combining Cerebello-spinal Neuromodulation and Exercise in Spinocerebellar Ataxia Type 3: A 20-session Single-arm Protocol.
Cerebellum (London, England)Extracellular vesicles-associated AAVs for the treatment of Machado-Joseph disease.
Molecular therapy : the journal of the American Society of Gene TherapyPeripheral inflammation in spinocerebellar ataxia type 3: associations with genetic and clinical manifestations.
Inflammation research : official journal of the European Histamine Research Society ... [et al.]Cerebello-cortical inhibition underlies the effects of cerebellar magnetic stimulation on spinocerebellar ataxia type 3: A randomized controlled trial.
Brain stimulationDysphagia linked to clinical phenotype and disease progression in spinocerebellar ataxia type 3.
European journal of medical researchArticle Title: Impact of Dysphagia on Quality of Life in Machado-Joseph Disease.
Cerebellum (London, England)Long-read sequencing identifies ATXN3 repeat expansions, and transcriptomics reveals disease progression biomarkers and druggable targets for spinocerebellar ataxia type 3.
BMC neurologyDistribution of perivascular spaces distribution and relate to the clinical features of SCA3.
Orphanet journal of rare diseasesAltered static and dynamic spontaneous brain activity patterns in spinocerebellar ataxia type3 patients.
Journal of neurologyCircadian rhythms are disrupted in patients and preclinical models of Machado-Joseph disease.
Brain : a journal of neurologyInfluence of ATXN2 intermediate CAG repeats, 9bp duplication and alternative splicing on SCA3 pathogenesis.
Acta neuropathologica communicationsProgressive subcortical involvement as spinocerebellar ataxia type 3 advances.
Orphanet journal of rare diseasesMachado-Joseph disease in Brazil and other South American countries: A systematic Review and Meta-analysis of Prevalence, CAG Repeat Lengths, Age At Onset, and Ancestry.
Cerebellum (London, England)Differential effects of lifespan-extending genetic manipulations in an animal model of MJD/SCA3.
Mechanisms of ageing and developmentGenome editing in spinocerebellar ataxia type 3 cells improves Golgi apparatus structure.
Scientific reportsLongitudinal description of health-related quality of life and depressive symptoms in polyQ spinocerebellar ataxia patients.
Journal of neurologyFatigue in the Preataxic and Ataxic Stages of Spinocerebellar Ataxia Type 3.
European journal of neurologyMovement Disorders in Hereditary Cerebellar Ataxia.
Movement disorders clinical practiceAssessment of Peripheral Neuropathy Using Current Perception Threshold Measurement in Patients with Spinocerebellar Ataxia Type 3.
Cerebellum (London, England)Associations between CAG repeat size, brain and spinal cord volume loss, and motor symptoms in spinocerebellar ataxia type 3: a cohort study.
Orphanet journal of rare diseasesStep Width Haptic Feedback for Gait Stability in Spinocerebellar Ataxia: Preliminary Results.
Movement disorders : official journal of the Movement Disorder SocietyWhite matter functional and structural alterations of spinocerebellar ataxia type 3: A longitudinal MRI study.
NeuroscienceApolipoprotein E epsilon4 allele is associated with better performance language and visual memory in spinocerebellar ataxia type 3.
European journal of neurologyRegional distribution of polymorphisms associated to the disease-causing gene of spinocerebellar ataxia type 3.
Journal of neurologySplit hand and minipolymyoclonus in spinocerebellar ataxia type 3: a case report.
BMC neurologyPotential Disease-Modifying Effects of Ganglioside GM1 Pulse Treatment on Spinocerebellar Ataxia Type 3, a Parallel-Group, Double-Blind, Randomized, Controlled Trial.
Movement disorders : official journal of the Movement Disorder SocietyAstragaloside IV reduces mutant Ataxin-3 levels and supports mitochondrial function in Spinocerebellar Ataxia Type 3.
Scientific reportsMorphological changes of cerebral gray matter in spinocerebellar ataxia type 3 using fractal dimension analysis.
Progress in brain researchPreimplantation Genetic Testing of Spinocerebellar Ataxia Type 3/Machado-Joseph Disease-Robust Tools for Direct and Indirect Detection of the ATXN3 (CAG)n Repeat Expansion.
International journal of molecular sciencesThe parkin V380L variant is a genetic modifier of Machado-Joseph disease with impact on mitophagy.
Acta neuropathologicaSpinocerebellar Ataxias: Phenotypic Spectrum of PolyQ versus Non-Repeat Expansion Forms.
Cerebellum (London, England)Single-Session Cerebellar Transcranial Direct Current Stimulation Improves Postural Stability and Reduces Ataxia Symptoms in Spinocerebellar Ataxia.
Cerebellum (London, England)Spermidine treatment: induction of autophagy but also apoptosis?
Molecular brainInvestigating the therapeutic effects of novel compounds targeting inflammatory IL-1β and IL-6 signaling pathways in spinocerebellar ataxia type 3.
European journal of pharmacologyThe natural breakthrough: phytochemicals as potent therapeutic agents against spinocerebellar ataxia type 3.
Scientific reportsEfficiency of PGK1 proteins delivered to the brain via a liposomal system through intranasal route administration for the treatment of spinocerebellar ataxia type 3.
Drug delivery and translational researchEfficacy and Safety of Repetitive Transcranial Magnetic Stimulation in Spinocerebellar Ataxia Type 3: a Systematic Review and Meta‑analysis of Randomized Controlled Trials.
Cerebellum (London, England)IL-4/STAT6 axis observed to reverse proliferative defect in SCA3 patient-derived neural progenitor cells.
Clinical and experimental pharmacology & physiologyPrevalence of repeat expansions causing autosomal dominant spinocerebellar ataxias in Hokkaido, the northernmost island of Japan.
Journal of human geneticsA pilot study: handgrip as a predictor in the disease progression of SCA3.
Orphanet journal of rare diseasesGenetic Epidemiology and Clinical Characteristics of Patients with Spinocerebellar Ataxias in an Unexplored Brazilian State, Using Strategies for Resource-Limited Settings.
Cerebellum (London, England)Genetic Ablation of Inositol 1,4,5-Trisphosphate Receptor Type 2 (IP3R2) Fails to Modify Disease Progression in a Mouse Model of Spinocerebellar Ataxia Type 3.
International journal of molecular sciencesTherapeutic effects of engineered exosome-based miR-25 and miR-181a treatment in spinocerebellar ataxia type 3 mice by silencing ATXN3.
Molecular medicine (Cambridge, Mass.)Efficacy of cerebellar transcranial magnetic stimulation in spinocerebellar ataxia type 3: a randomized, single-blinded, controlled trial.
Journal of neurologyImplications of specific lysine residues within ataxin-3 for the molecular pathogenesis of Machado-Joseph disease.
Frontiers in molecular neuroscienceThe longitudinal progression of MRI changes in pre-ataxic carriers of SCA3/MJD.
Journal of neurologyEffectiveness of High-Frequency Repetitive Transcranial Magnetic Stimulation in Patients With Spinocerebellar Ataxia Type 3.
The journal of ECTSynaptic Loss in Spinocerebellar Ataxia Type 3 Revealed by SV2A Positron Emission Tomography.
Movement disorders : official journal of the Movement Disorder SocietyHorizontal Vestibulo-Ocular Reflex Deficit as a Biomarker for Clinical Disease Onset, Severity, and Progression of Machado-Joseph Disease.
Cerebellum (London, England)Outcomes with Finerenone in Participants with Stage 4 CKD and Type 2 Diabetes: A FIDELITY Subgroup Analysis.
Clinical journal of the American Society of Nephrology : CJASNBaseline Clinical and Blood Biomarkers in Patients With Preataxic and Early-Stage Disease Spinocerebellar Ataxia 1 and 3.
NeurologyRetinal Manifestations in Spinocerebellar Ataxia Type 3.
Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology SocietyAltered binaural hearing in pre-ataxic and ataxic mutation carriers of spinocerebellar ataxia type 3.
Cerebellum (London, England)Association Between Serum Neurofilament Light Chain and Neurochemistry Deficits in Patients with Spinocerebellar Ataxia Type 3.
Cerebellum (London, England)The protective effect of erinacine A-enriched Hericium erinaceus mycelium ethanol extract on oxidative Stress-Induced neurotoxicity in cell and Drosophila models of spinocerebellar ataxia type 3.
Free radical biology & medicineEffect of speech therapy on quality of life in patients with spinocerebelar ataxia type 3.
Arquivos de neuro-psiquiatriaThe stress granule protein G3BP1 alleviates spinocerebellar ataxia-associated deficits.
Brain : a journal of neurologyMachado Joseph-Disease Is Rare in the Peruvian Population.
Cerebellum (London, England)Characterization of the central motor conduction time in a large cohort of spinocerebellar ataxia type 3 patients.
Parkinsonism & related disordersProgression of Clinical and Eye Movement Markers in Preataxic Carriers of Machado-Joseph Disease.
Movement disorders : official journal of the Movement Disorder SocietyExplainable artificial intelligence based on feature optimization for age at onset prediction of spinocerebellar ataxia type 3.
Frontiers in neuroinformaticsCoenzyme Q10 Supplementation Increases Removal of the ATXN3 Polyglutamine Repeat, Reducing Cerebellar Degeneration and Improving Motor Dysfunction in Murine Spinocerebellar Ataxia Type 3.
NutrientsDigital Gait Biomarkers Allow to Capture 1-Year Longitudinal Change in Spinocerebellar Ataxia Type 3.
Movement disorders : official journal of the Movement Disorder SocietyDerivation of spinocerebellar ataxia type 3 human embryonic stem cell line UMICHe001-A/UM134-1.
Stem cell researchShort Communication: Restrictions in care following the COVID-19 pandemic severely impacted Machado-Joseph disease patients: a study in the Azores Islands, Portugal.
Journal of community geneticsEstablishment and characterization of human pluripotent stem cells-derived brain organoids to model cerebellar diseases.
Scientific reportsThe Natural History of Spinocerebellar Ataxia Type 3 in Mainland China: A 2-Year Cohort Study.
Frontiers in aging neuroscienceDifferential Temporal Dynamics of Axial and Appendicular Ataxia in SCA3.
Movement disorders : official journal of the Movement Disorder SocietyKPNB1 modulates the Machado-Joseph disease protein ataxin-3 through activation of the mitochondrial protease CLPP.
Cellular and molecular life sciences : CMLSBody sway and movement strategies for control of postural stability in people with spinocerebellar ataxia type 3: A cross-sectional study.
Clinical biomechanics (Bristol, Avon)CRISPR/Cas9-mediated genetic correction reverses spinocerebellar ataxia 3 disease-associated phenotypes in differentiated cerebellar neurons.
Life medicineMitochondrial Dysfunction in Spinocerebellar Ataxia Type 3 Is Linked to VDAC1 Deubiquitination.
International journal of molecular sciencesCerebellar transcranial direct current stimulation modulates timing but not acquisition of conditioned eyeblink responses in SCA3 patients.
Brain stimulationThe progression rate of spinocerebellar ataxia type 3 varies with disease stage.
Journal of translational medicineAltered glucose metabolism and its association with carbonic anhydrase 8 in Machado-Joseph Disease.
Metabolic brain diseaseTau and neurofilament light-chain as fluid biomarkers in spinocerebellar ataxia type 3.
European journal of neurologyDiagnostic efficacy of the magnetic resonance T1w/T2w ratio for the middle cerebellar peduncle in multiple system atrophy and spinocerebellar ataxia: A preliminary study.
PloS onePlasma PolyQ-ATXN3 Levels Associate With Cerebellar Degeneration and Behavioral Abnormalities in a New AAV-Based SCA3 Mouse Model.
Frontiers in cell and developmental biologyCerebellar morphometric and spectroscopic biomarkers for Machado-Joseph Disease.
Acta neuropathologica communicationsDNA methylation age acceleration is associated with age of onset in Chinese spinocerebellar ataxia type 3 patients.
Neurobiology of agingAnti-Excitotoxic Effects of N-Butylidenephthalide Revealed by Chemically Insulted Purkinje Progenitor Cells Derived from SCA3 iPSCs.
International journal of molecular sciencesApraxia of Eyelid Opening and Blepharospasm in Two Spinocerebellar Ataxia Type 3 Patients.
Tremor and other hyperkinetic movements (New York, N.Y.)Finerenone in Patients With Chronic Kidney Disease and Type 2 Diabetes According to Baseline HbA1c and Insulin Use: An Analysis From the FIDELIO-DKD Study.
Diabetes careGenetic Variation in ATXN3 (Ataxin-3) 3'UTR: Insights into the Downstream Regulatory Elements of the Causative Gene of Machado-Joseph Disease/Spinocerebellar Ataxia Type 3.
Cerebellum (London, England)Preclinical Assessment of Mesenchymal-Stem-Cell-Based Therapies in Spinocerebellar Ataxia Type 3.
BiomedicinesOuter Retinal Disruption in Spinocerebellar Ataxia Type 1.
Ophthalmology. RetinaA Novel SCA3 Knock-in Mouse Model Mimics the Human SCA3 Disease Phenotype Including Neuropathological, Behavioral, and Transcriptional Abnormalities Especially in Oligodendrocytes.
Molecular neurobiologyA Novel Calpain Inhibitor Compound Has Protective Effects on a Zebrafish Model of Spinocerebellar Ataxia Type 3.
CellsCRISPR/Cas9 mediated gene correction ameliorates abnormal phenotypes in spinocerebellar ataxia type 3 patient-derived induced pluripotent stem cells.
Translational psychiatryExploring the clinical meaningfulness of the Scale for the Assessment and Rating of Ataxia: A comparison of patient and physician perspectives at the item level.
Parkinsonism & related disordersThe autophagy-enhancing drug carbamazepine improves neuropathology and motor impairment in mouse models of Machado-Joseph disease.
Neuropathology and applied neurobiologyPattern of cerebellar grey matter loss associated with ataxia severity in spinocerebellar ataxias type 3: a multi-voxel pattern analysis.
Brain imaging and behaviorSodium valproate increases activity of the sirtuin pathway resulting in beneficial effects for spinocerebellar ataxia-3 in vivo.
Molecular brainTranscriptomic and Metabolic Network Analysis of Metabolic Reprogramming and IGF-1 Modulation in SCA3 Transgenic Mice.
International journal of molecular sciencesUrine levels of the polyglutamine ataxin-3 protein are elevated in patients with spinocerebellar ataxia type 3.
Parkinsonism & related disordersULK overexpression mitigates motor deficits and neuropathology in mouse models of Machado-Joseph disease.
Molecular therapy : the journal of the American Society of Gene TherapyIdentification of the calpain-generated toxic fragment of ataxin-3 protein provides new avenues for therapy of Machado-Joseph disease| Spinocerebellar ataxia type 3.
Neuropathology and applied neurobiologyQuality of Life since Pre-Ataxic Phases of Spinocerebellar Ataxia Type 3/Machado-Joseph Disease.
Cerebellum (London, England)Dataset on the effect of Rubicon overexpression on polyglutamine-induced locomotor dysfunction in Drosophila.
Data in briefDNAzyme Cleavage of CAG Repeat RNA in Polyglutamine Diseases.
Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeuticsChronic use of renin-angiotensin-aldosterone system blockers and mortality in COVID-19: A multicenter prospective cohort and literature review.
Fundamental & clinical pharmacologySARS-CoV-2 vaccination modelling for safe surgery to save lives: data from an international prospective cohort study.
The British journal of surgeryNeurodegenerative phosphoprotein signaling landscape in models of SCA3.
Molecular brainAbnormal eye movements in spinocerebellar ataxia type 3.
BMC neurologySelective forces acting on spinocerebellar ataxia type 3/Machado-Joseph disease recurrency: A systematic review and meta-analysis.
Clinical geneticsPathomechanism characterization and potential therapeutics identification for SCA3 targeting neuroinflammation.
AgingDeubiquitinase USP7 contributes to the pathogenicity of spinal and bulbar muscular atrophy.
The Journal of clinical investigationNeurotherapeutic effect of Hyptis spp. leaf extracts in Caenorhabditis elegans models of tauopathy and polyglutamine disease: Role of the glutathione redox cycle.
Free radical biology & medicineCapturing the Conformational Ensemble of the Mixed Folded Polyglutamine Protein Ataxin-3.
Structure (London, England : 1993)Familial spontaneous pneumothorax and Machado-Joseph disease.
Oxford medical case reportsEffects of Rivastigmine on Patients with Spinocerebellar Ataxia Type 3: A Case Series of Five Patients.
Neuro-degenerative diseasesPrediction of the Age at Onset of Spinocerebellar Ataxia Type 3 with Machine Learning.
Movement disorders : official journal of the Movement Disorder SocietyCAG Repeat Size Influences the Progression Rate of Spinocerebellar Ataxia Type 3.
Annals of neurologyWhich Factors in Spinocerebellar Ataxia Type 3 Patients Are Associated with Restless Legs Syndrome/Willis-Ekbom Disease?
Cerebellum (London, England)Effects of cerebellar transcranial magnetic stimulation on ataxias: A randomized trial.
Parkinsonism & related disordersCorticospinal tract involvement in spinocerebellar ataxia type 3: a diffusion tensor imaging study.
NeuroradiologyThe blood-brain barrier is disrupted in Machado-Joseph disease/spinocerebellar ataxia type 3: evidence from transgenic mice and human post-mortem samples.
Acta neuropathologica communicationsGenotype-phenotype correlation in 667 Chinese families with spinocerebellar ataxia type 3.
Parkinsonism & related disordersAntisense Oligonucleotide Therapy Targeted Against ATXN3 Improves Potassium Channel-Mediated Purkinje Neuron Dysfunction in Spinocerebellar Ataxia Type 3.
Cerebellum (London, England)Ubiquilin-2 differentially regulates polyglutamine disease proteins.
Human molecular geneticsFactors Associated with Intergenerational Instability of ATXN3 CAG Repeat and Genetic Anticipation in Chinese Patients with Spinocerebellar Ataxia Type 3.
Cerebellum (London, England)Inclusion body myositis in patients with spinocerebellar ataxia types 3 and 6.
Journal of neurology, neurosurgery, and psychiatryA 5-Year Longitudinal Clinical and Magnetic Resonance Imaging Study in Spinocerebellar Ataxia Type 3.
Movement disorders : official journal of the Movement Disorder SocietyReconstructing the History of Machado-Joseph Disease.
European neurologyVertical pons hyperintensity and hot cross bun sign in cerebellar-type multiple system atrophy and spinocerebellar ataxia type 3.
BMC neurologySpinocerebellar Atrophy Type-3 with Chiari Malformation in a Young Man: A Case Report.
Advanced journal of emergency medicineDistribution of the CAG Triplet Repeat in ATXN1, ATXN3, and CACNA1A Loci in Peruvian Population.
Cerebellum (London, England)Global Knockdown of Retinoid-related Orphan Receptor α in Mature Purkinje Cells Reveals Aberrant Cerebellar Phenotypes of Spinocerebellar Ataxia.
NeuroscienceTrehalose alleviates the phenotype of Machado-Joseph disease mouse models.
Journal of translational medicineThe impact of ethnicity on the clinical presentations of spinocerebellar ataxia type 3.
Parkinsonism & related disordersDruggable genome screen identifies new regulators of the abundance and toxicity of ATXN3, the Spinocerebellar Ataxia type 3 disease protein.
Neurobiology of diseaseAlternating monocular adducting saccadic pulses and dissociated adducting nystagmus during lateral gazes in spinocerebellar ataxia type 3.
Journal of neurologyNeurofilament light chain is a promising serum biomarker in spinocerebellar ataxia type 3.
Molecular neurodegenerationThe Machado-Joseph disease deubiquitylase ataxin-3 interacts with LC3C/GABARAP and promotes autophagy.
Aging cellGene-Related Cerebellar Neurodegeneration in SCA3/MJD: A Case-Controlled Imaging-Genetic Study.
Frontiers in neurologyVariation in DNA Repair System Gene as an Additional Modifier of Age at Onset in Spinocerebellar Ataxia Type 3/Machado-Joseph Disease.
Neuromolecular medicineSpinocerebellar ataxias in Southern Brazil: Genotypic and phenotypic evaluation of 213 families.
Clinical neurology and neurosurgeryDifferential toxicity of ataxin-3 isoforms in Drosophila models of Spinocerebellar Ataxia Type 3.
Neurobiology of diseaseSelection of Reference Genes for Normalization of Gene Expression Data in Blood of Machado-Joseph Disease/Spinocerebellar Ataxia Type 3 (MJD/SCA3) Subjects.
Journal of molecular neuroscience : MNCerebellar transcranial direct current stimulation in spinocerebellar ataxia type 3 (SCA3-tDCS): rationale and protocol of a randomized, double-blind, sham-controlled study.
BMC neurologyRNA Expression Profile and Potential Biomarkers in Patients With Spinocerebellar Ataxia Type 3 From Mainland China.
Frontiers in geneticsPrediction of Survival With Long-Term Disease Progression in Most Common Spinocerebellar Ataxia.
Movement disorders : official journal of the Movement Disorder SocietyProtective roles of carbonic anhydrase 8 in Machado-Joseph Disease.
Journal of neuroscience researchIdentification of a potential exosomal biomarker in spinocerebellar ataxia Type 3/Machado-Joseph disease.
EpigenomicsAssociation between restless legs syndrome and other movement disorders.
NeurologyIs the High Frequency of Machado-Joseph Disease in China Due to New Mutational Origins?
Frontiers in geneticsRNA Interference Therapy for Machado-Joseph Disease: Long-Term Safety Profile of Lentiviral Vectors Encoding Short Hairpin RNAs Targeting Mutant Ataxin-3.
Human gene therapyAssessment of Bone Mineral Density of Patients with Spinocerebellar Ataxia Type 3.
Journal of movement disordersFipoQ/FBXO33, a Cullin-1-based ubiquitin ligase complex component modulates ubiquitination and solubility of polyglutamine disease protein.
Journal of neurochemistryTargeting Ubiquitin Proteasome Pathway with Traditional Chinese Medicine for Treatment of Spinocerebellar Ataxia Type 3.
The American journal of Chinese medicineIdentification of 35 CAG repeats within ATXN1 as the probable shortest pathogenic allele for spinalcerebellar ataxia type 1.
Journal of the neurological sciencesPharmacological enhancement of retinoid-related orphan receptor α function mitigates spinocerebellar ataxia type 3 pathology.
Neurobiology of diseaseInhibition of NF-κB in astrocytes is sufficient to delay neurodegeneration induced by proteotoxicity in neurons.
Journal of neuroinflammationUpregulation of miR-25 and miR-181 Family Members Correlates with Reduced Expression of ATXN3 in Lymphocytes from SCA3 Patients.
MicroRNA (Shariqah, United Arab Emirates)Diagnostic Challenges Posed by Preceding Peripheral Neuropathy in Very Late-onset Spinocerebellar Ataxia Type 3.
Internal medicine (Tokyo, Japan)Age at onset prediction in spinocerebellar ataxia type 3 changes according to population of origin.
European journal of neurologyUpregulation of miR-370 and miR-543 is associated with reduced expression of heat shock protein 40 in spinocerebellar ataxia type 3.
PloS oneDystonia in Patients with Spinocerebellar Ataxia 3 - Machado-Joseph disease: An Underestimated Diagnosis?
The open neurology journalMachado-Joseph disease/spinocerebellar ataxia type 3: lessons from disease pathogenesis and clues into therapy.
Journal of neurochemistryTranscriptional profiling and biomarker identification reveal tissue specific effects of expanded ataxin-3 in a spinocerebellar ataxia type 3 mouse model.
Molecular neurodegenerationOlfactory Function in SCA10.
Cerebellum (London, England)Oligonucleotide therapy mitigates disease in spinocerebellar ataxia type 3 mice.
Annals of neurologyAtaxin-3 promotes testicular cancer cell proliferation by inhibiting anti-oncogene PTEN.
Biochemical and biophysical research communicationsA randomized controlled pilot trial of game-based training in individuals with spinocerebellar ataxia type 3.
Scientific reportsBody composition in Spinocerebellar ataxia type 3 and 10 patients: Comparative study with control group.
Nutritional neuroscienceFar-infrared Radiation Improves Motor Dysfunction and Neuropathology in Spinocerebellar Ataxia Type 3 Mice.
Cerebellum (London, England)Accumulation of Mitochondrial DNA Common Deletion Since The Preataxic Stage of Machado-Joseph Disease.
Molecular neurobiologyA diagnostic decision tree for adult cerebellar ataxia based on pontine magnetic resonance imaging.
Journal of the neurological sciencesNeuroprotective Effects of Creatine in the CMVMJD135 Mouse Model of Spinocerebellar Ataxia Type 3.
Movement disorders : official journal of the Movement Disorder SocietyThe Neuropathology of Spinocerebellar Ataxia Type 3/Machado-Joseph Disease.
Advances in experimental medicine and biology"Pinball" intrusions in spinocerebellar ataxia type 3.
NeurologySequence configuration of spinocerebellar ataxia type 8 repeat expansions in a Japanese cohort of 797 ataxia subjects.
Journal of the neurological sciencesTreatment with Caffeic Acid and Resveratrol Alleviates Oxidative Stress Induced Neurotoxicity in Cell and Drosophila Models of Spinocerebellar Ataxia Type3.
Scientific reportsPromoter Variant Alters Expression of the Autophagic BECN1 Gene: Implications for Clinical Manifestations of Machado-Joseph Disease.
Cerebellum (London, England)The Truncated C-terminal Fragment of Mutant ATXN3 Disrupts Mitochondria Dynamics in Spinocerebellar Ataxia Type 3 Models.
Frontiers in molecular neuroscienceArginine vasopressin relates with spatial learning and memory in a mouse model of spinocerebellar ataxia type 3.
NeuropeptidesCancer in Machado-Joseph disease patients-low frequency as a cause of death.
Cancer geneticsInteraction of the polyglutamine protein ataxin-3 with Rad23 regulates toxicity in Drosophila models of Spinocerebellar Ataxia Type 3.
Human molecular geneticsProteolytic Cleavage of Polyglutamine Disease-Causing Proteins: Revisiting the Toxic Fragment Hypothesis.
Current pharmaceutical designDysregulation of the endocannabinoid signaling system in the cerebellum and brainstem in a transgenic mouse model of spinocerebellar ataxia type-3.
NeuroscienceMotor cortical dysfunction develops in spinocerebellar ataxia type 3.
Clinical neurophysiology : official journal of the International Federation of Clinical NeurophysiologyInduced pluripotent stem cell - derived neurons for the study of spinocerebellar ataxia type 3.
Stem cell researchVestibulo-ocular reflex dynamics with head-impulses discriminates spinocerebellar ataxias types 1, 2 and 3 and Friedreich ataxia.
Journal of vestibular research : equilibrium & orientationFibroblasts of Machado Joseph Disease patients reveal autophagy impairment.
Scientific reportsParametric fMRI of paced motor responses uncovers novel whole-brain imaging biomarkers in spinocerebellar ataxia type 3.
Human brain mappingPromoter Variation and Expression Levels of Inflammatory Genes IL1A, IL1B, IL6 and TNF in Blood of Spinocerebellar Ataxia Type 3 (SCA3) Patients.
Neuromolecular medicineFatigue and Its Associated Factors in Spinocerebellar Ataxia Type 3/Machado-Joseph Disease.
Cerebellum (London, England)In vivo assessment of riluzole as a potential therapeutic drug for spinocerebellar ataxia type 3.
Journal of neurochemistryPearls & Oy-sters: Spinocerebellar ataxia type 3 presenting with cervical dystonia without ataxia.
NeurologyA Tandem Oligonucleotide Approach for SNP-Selective RNA Degradation Using Modified Antisense Oligonucleotides.
PloS oneAssociações
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Referências e fontes
Bases de dados externas citadas neste artigo
Publicações científicas
Artigos indexados no PubMed ligados a esta doença no grafo RarasNet — título, periódico e PMID direto da fonte, sem intermediação de IA.
- Gastrodin inhibits the formation of ataxin-3 aggregates by regulating the level of ERK1/2/P38 proteins.
- Peripheral and autonomic nervous system involvement in spinocerebellar ataxia type 3: unveiling an invisible burden.
- Investigating the pathogenic role of calpain proteases and the therapeutic potential of their inhibition in mice modelling Machado-Joseph disease.
- Extracellular vesicles-associated AAVs for the treatment of Machado-Joseph disease.Molecular therapy : the journal of the American Society of Gene Therapy· 2026· PMID 41077785mais citado
- IGFBP1 as a metabolic-neurodegenerative biomarker in spinocerebellar ataxia type 3.
- Extracellular vesicles-mediated delivery of SpCas9 RNPs for therapeutic gene editing in Spinocerebellar Ataxia Type 3.
- Revisited case for intranasal neuropeptide Y based therapeutics: From preclinical to clinical.
- Retrotransposition Events Shape the Evolution of the Ataxin-3 Gene Family in Primates.
Bases de dados e fontes oficiais
Identificadores e referências canônicas usadas para montar este verbete.
- ORPHA:276238(Orphanet)
- MONDO:0017174(MONDO)
- GARD:21048(GARD (NIH))
- Variantes catalogadas(ClinVar)
- Busca completa no PubMed(PubMed)
- Q55345982(Wikidata)
Dados compilados pelo RarasNet a partir de fontes abertas (Orphanet, OMIM, MONDO, PubMed/EuropePMC, ClinicalTrials.gov, DATASUS, PCDT/MS). Este conteúdo é informativo e não substitui avaliação médica.
Conteúdo mantido por Agente Raras · Médicos e pesquisadores podem colaborar